Diagnosis and differential diagnosis of multiple sclerosis.
The diagnostic criteria for MS have been revised several times over the years, most recently giving rise to the McDonald 2010 criteria. The diagnosis of MS begins with a patient who presents with symptoms typical for the disease, termed the "clinically isolated syndrome," which most commonly affects the optic nerves, brainstem, or spinal cord. If the patient's symptoms and imaging are typical for MS, the clinician can then apply the appropriate diagnostic criteria. If atypical clinical or imaging findings are present, alternative etiologies must be pursued as appropriate

T-cell homeostasis in pediatric multiple sclerosis: old cells in young patients.
The homeostatic changes detected in the T-cell compartment in pMS are similar to those in adult-onset disease. With ratios between naive and memory T-cell subsets matching those of 20- to 30-years-older controls, signs of early thymic involution are already found in pMS, suggesting that an intrinsic compromise in thymic-dependent T-cell neogenesis might contribute to MS pathogenesis.

Strategies for protecting oligodendrocytes and enhancing remyelination in multiple sclerosis.
Combining immunomodulatory therapy with strategies to protect oligodendrocytes from further degeneration and enhance remyelination presents a very real means to improve clinical outcome for chronic progressive patients in the near future. Here we lay out a combination therapy approach to treating MS and survey the current literature on promising drug candidates potentially capable of mediating oligodendrocyte protection and enhancing remyelination.

Comorbidities at multiple sclerosis diagnosis.
The mean age at request for ALD status for MS in patients with no comorbidity was 33.6 ± 7.2 years, whereas it was 36.9 ± 6.5 years in those with comorbidities. Comorbidities at MS notification are rare. Psychiatric disorders and diabetes were more frequent in MS patients than in the general population.

Serum vitamin d levels in Indian patients with multiple sclerosis.
An age-matched control group of 202 patients who did not have a diagnosis of MS were included. In our study group 76.9 % had vitamin D level less than 20 ng/ml compared to 65.5 % of control group (p value of 0.019). Our study revealed a trend towards low vitamin D values in Indian MS patients.

Revised Diagnostic Criteria of Multiple Sclerosis.
The most recent 2010 McDonald criteria simplify requirements for DIS and DIT and may allow for an earlier diagnosis of MS from a single baseline brain MRI if there are both silent gadolinium-enhancing and nonenhancing lesions. Despite these important advances in the diagnosis of MS, some questions still remain regarding the application and the implications of the new criteria in the daily clinical practice and in clinical trials. Most importantly, thorough clinical evaluation and judgment along with careful differential diagnosis still remain the basics in the diagnosis of MS.

Intrathecal immune reset in multiple sclerosis: Exploring a new concept.
We review the literature in support of the rationale for treating MS with intrathecal drugs dedicated to clearing the local immune response. Since many targets are involved, achieving this goal may require a combination of monoclonal antibodies targeting each cell sub-type. Hope might be rekindled with a one-shot intrathecal multi-drug treatment in progressive MS.

Protective and Detrimental Roles for Regulatory T Cells in a Viral Model for Multiple Sclerosis.
The exacerbation of acute disease was associated with increased virus titers and decreased immune cell recruitment in the CNS. Therapeutic iTreg treatment reduced inflammatory demyelination during chronic disease. Immunologically, iTreg treatment increased interleukin-10 production from B cells, CD4+ T cells, and dendritic cells, which may contribute to the decreased CNS inflammation.

Confounding in association studies: month of birth and multiple sclerosis.
In this review, we will illustrate these fundamental issues by considering the previously proposed relationship between month of birth and multiple sclerosis. This much discussed but false positive association serves as a reminder of just how heterogeneous even easily measured environmental risk factors can be, and how easily case control studies can be confounded by seemingly minor differences in ascertainment.

Alcohol and substance use in multiple sclerosis.
Current alcohol use was prevalent in this sample, and excessive use was associated with men, younger age, and more education. Reported drug use was minimal and associated with greater disability, more self-reported depression, but fewer anxiety symptoms.

Disease course heterogeneity and OCT in multiple sclerosis.
The thicknesses, particularly of the innermost retinal layers (RNFL, GCC), were significantly related to the heterogeneous disease course in MS. The relative preservation of these layers in primary progressive and benign MS suggests rather limited susceptibility of the retina to neurodegeneration, which may be relevant for future neurodegenerative treatment trials employing OCT as a secondary outcome measure in primary progressive MS.

Pseudobulbar affect (PBA): prevalence and management.
A recent therapeutic breakthrough occurred with the approval by the Food and Drug Administration of a dextromethorphan/quinidine combination as being safe and effective for treatment of PBA. Side effect profiles and contraindications differ for the various treatment options, and the clinician must be familiar with these when choosing the best therapy for an individual, particularly elderly patients and those with multiple comorbidities and concomitant medications.

Body composition in multiple sclerosis.
Body mass index values, the effect of spasticity, the increased number of drugs used and the relationship between skeletal muscle and bone which interacts with impaired motor function leading to body composition alterations in multiple sclerosis are reviewed.

Modeling of cognitive impairment by disease duration in multiple sclerosis: a cross-sectional study.
The rates of cognitive impairment in this large sample of MS patients were lower than previously reported and severe cognitive impairment was evident only in a relatively small group of patients. Cognitive impairment differed significantly from expected normal distribution only at five years from onset, suggesting the existence of a therapeutic window during which patients may benefit from interventions to maintain cognitive health.

1H magnetic resonance spectroscopy in multiple sclerosis and related disorders.
In this review article we present the main brain and spinal cord (1)H-MRS features in MS, their diagnostic value in differentiating pseudotumoral demyelinating lesions from primary brain tumors, and their relationship with clinical variables. Last, some data related to the use of (1)H-MRS in therapeutic trials is presented.

Coexistence of multiple sclerosis and ankylosing spondylitis: report of two cases.
The remaining effective therapeutic options for MS are either contradictory for AS (interferon-β), have no definite data regarding their safety/efficacy in AS (glatiramer acetate, azathioprine, natalizumab, fingolimod), or their efficacy in MS-AS is associated with increased treatment risks (rituximab). Any of these proposed treatments may require active patient's informed consent.

Improved Characterization of Visual Evoked Potentials in Multiple Sclerosis by Topographic Analysis.
Sensitivity was increased in tVEP versus cVEP: 72 % versus 60 % for diagnosis, and 88 % versus 77 % for hON. The advantage of tVEP was most pronounced in pathological VEPs, in which cVEPs were often ambiguous. TVEP is a reliable, valid, and sensitive method of objectively quantifying pathological VEP in particular. In combination with other EP modalities, tVEP may improve the monitoring of disease course in MS.

Remyelination therapy for multiple sclerosis.
The next frontier in MS therapeutics will supplement immunomodulation with agents that directly foster myelin repair, with aims to delay disease progression and recover lost neurological functions.

Cerebrospinal fluid biomarkers of β-amyloid metabolism in multiple sclerosis.
We confirmed and extended our previous observations of altered CSF sAPP and Aβ peptide levels in MS patients. We found that natalizumab therapy may be able to counteract the altered APP metabolism in MS. The CSF Aβ isoform distribution was found to be distinct in SPMS patients, as compared to the controls.

Daclizumab therapy for multiple sclerosis.
In conclusion, daclizumab therapy, which is currently in phase III testing for inflammatory MS, has a unique MOA that does not limit migration of immune cells into the intrathecal compartment, but rather provides multifactorial immunomodulatory effects with resultant inhibition of MS-related inflammation.

Reducing survey burden: feasibility and validity of PROMIS measures in multiple sclerosis.
Our results provide evidence of the construct validity of PROMIS for use with MS patients. Several aspects of the PROMIS CATs made them an important resource, including: (a) less time was required to complete them; (b) missing data was reduced; and (c) the automatic scoring referenced the general population. Our findings support the use of PROMIS in MS research and may have broader implications for clinical care, as well.

Estimating time to disease progression comparing transition models and survival methods--an analysis of multiple sclerosis data.
This article compares the transition model approach to survival analysis methods, and discusses the differences in the interpretations of the estimated parameters. It applies both models to data obtained from two phase 3 clinical trials and finds that both yield positive effects for the new treatment compared to placebo, and provide similar estimates for the probability of disability progression over time. The transition model enables calculation of covariate-specific transition matrices that describe the short-term effect of treatment and other covariates on the disability process.

Vagus somatosensory-evoked potentials are prolonged in patients with multiple sclerosis with brainstem involvement.
A subgroup of patients with signs of brainstem affection showed a trend for longer P1 latencies (F(1,11)=5916, P=0.033) as compared with the group without. We take this result as further hint for VSEP to be generated at brainstem level which needs confirmation in larger-scale studies and other brainstem-affecting diseases. The method could be suitable for the demonstration of the involvement of differential brainstem nuclei in various neurodegenerative diseases.

Multiple sclerosis and the blood-central nervous system barrier.
The MS drug natalizumab, a humanized monoclonal antibody against α4-β1-integrin, blocks this interaction and thus reduces the movement of immune cells into the CNS. This paper further elaborates on the role of the BCNSB in the pathophysiology and pharmacotherapy of MS

SIRT1 is decreased during relapses in patients with multiple sclerosis.
we investigated the role of SIRT1 in the expression of FasL and found a significant increase in FasL expression and apoptosis after inhibition of SIRT1 expression. Our data suggest that SIRT1 may represent a biomarker of relapses and a potential new target for therapeutic intervention in MS.

Iron chelation and multiple sclerosis.
More recently developed chelators, deferasirox and deferiprone, are more desirable for possible use in MS given their oral administration, and importantly, deferiprone can cross the blood-brain barrier. However, experiences from other conditions indicate that the potential for adverse events during chelation therapy necessitates close patient monitoring and a carefully considered administration regimen.

Vitamin D in multiple sclerosis: implications for assessment and treatment.
the authors advise that the serum concentration of 25-hydroxyvitamin D is monitored in order to prevent bone deficit, and that a serum level of 75-125 nmol/l is targeted. This level is sufficient for maintenance of bone health, is not known to be associated with adverse events, and is in the range that has been associated with low risk of developing MS and low disease activity.

Behavioral interventions in multiple sclerosis: a biopsychosocial perspective.
recent evidence suggests that group education or face-to-face behavioral interventions may decrease inflammatory disease activity (such as relapse rate or lesion formation measured by MRI). Therefore, behavioral interventions not only ameliorate symptoms but may have the potential to modify the disease process itself.

Increased HLA-E expression in white matter lesions in multiple sclerosis.
These results suggest the potential for an effect in central nervous system pathogenesis from HLA-E modulation in stressed tissue. Co-localization with infiltrating CD8+ cells implicates a possible role for HLA-E-restricted regulatory CD8+ cells, as has been proposed in other autoimmune diseases.

Transcriptional profiling of microdissected areas of active multiple sclerosis lesions reveals activation of heat shock protein genes.
To identify changes in HSP genes in relation to different areas of the plaque, we used genome-wide microarray analysis. We detected a significant change in the transcriptional profile of the demyelinated region compared with NAWM. In particular, overall expression of different HSP genes was upregulated in different areas of chronic-active lesion. These changes were linked to an upregulation of heat shock factor 4 (HSF4). This is the first global analysis of transcriptional changes in HSPs in the central nervous system during MS. The results support a relationship between HSP activation and lesion activity.

Cognitive impairment in neuro-Behcet's disease and multiple sclerosis: a comparative study.
In California Verbal Learning Test, both short- and long-term delayed recall and cued recognition were worse in neuro-Behcet's cases. They had impaired semantic clustering and increased false positives. Stroop Test was also more impaired in neuro-Behcet's cases. They needed significantly more trials to complete the first category of the Wisconsin Card Sorting Test and had a poorer total Frontal Behavioral Inventory Score. Our results suggest that neuro-Behcet's patients have a more severe "frontal"-executive dysfunction than MS patients.

Effect of gender on late-onset multiple sclerosis.
Women with LOMS have a different trajectory in terms of disease progression than women with AOMS. The effect of menopause combined with race/ethnicity on the MS disease course requires further investigation.

Il-17 And Glutamte Excitotoxicity In The Pathogenesis Of Multiple Sclerosis.
The results suggest that Th17 cells might enhance and use glutamate excitotoxicity as an effector mechanism in the MS pathogenesis. Furthermore, Th17 immune response, as well as neutrophils, could be more important for MS onset rather than further disease development and progression, what could explain why some MS clinical trials, targeting Th17 cells in the later stage of the disease, failed to provide any clinical benefit.

Surgery and risk for multiple sclerosis: a systematic review and meta-analysis of case-control studies.
We found a small but statistically significant and clinically important increased risk for developing multiple sclerosis, in those with tonsillectomy and appendectomy at ≤ 20 years of age. There was no convincing evidence to support the association of other surgeries and the risk for multiple sclerosis. Well-designed prospective etiological studies, pertaining to the risk for developing multiple sclerosis, ought to be conducted and should include the examination of various surgeries as risk factors.

Neural networks to identify multiple sclerosis with optical coherence tomography.
Compared with the OCT-provided parameters, the ANN had the largest area under the ROC curve. Conclusions: Measurements of RNFL thickness obtained with Spectralis OCT have a good ability to differentiate between healthy and individuals with multiple sclerosis. Based on the area under the ROC curve, the ANN performed better than any single OCT parameter.

Combining self-help and professional help to minimize barriers to physical activity in persons with multiple sclerosis: a trial of the "Blue Prescription" approach in New Zealand.
Evidence indicated that the Blue Prescription approach can provide a collaborative and flexible way for physical therapists to work with individuals with MS, to increase participation in community-based physical activity. To further develop the approach, there is a need to address issues related to the use of standardized measures and develop strategies to train physical therapists in collaborative approaches for promotion of physical activity.The integration of self-help and professional help provided by the Blue Prescription approach appeared to result in successful promotion of physical activity in persons with MS. Additional testing is required to examine its efficacy in other health care systems, in conditions beyond MS, and in terms of its economic impact.

Modelling the cost effectiveness of disease-modifying treatments for multiple sclerosis: issues to consider.
the cost effectiveness of DMTs outside North America and Europe is currently unknown, with the lack of country-specific data as the major limiting factor. We suggest that limited data should not preclude analyses, as models may be built and updated in the future as data become available. Disclosure of modelling methods and assumptions could improve the transferability and applicability of models designed to reflect different healthcare systems.

Baseline gene expression signatures in monocytes from multiple sclerosis patients treated with interferon-beta.
Purified monocytes from IFNb non-responders were characterized by an over-expression of type I IFN responsive genes, which confirms the type I IFN signature in monocytes suggested from previous studies. Other relevant signaling pathways that were up-regulated in IFNb non-responders were related with the mitochondrial function and processes such as protein synthesis and antigen presentation, and together with the type I IFN signaling pathway, may also be playing roles in the response to IFNb.

Factors influencing healthy aging with multiple sclerosis: a qualitative study.
This two-tiered conceptual model of health aging, based on the perspectives of older persons with MS, provides a potential framework for the development of MS self-management program curricula aimed at optimizing quality of life. Further empirical testing may validate its utility in predicting healthy aging with MS.

Patterns of dietary and herbal supplement use by multiple sclerosis patients.
The proportion of controls and MS patients after MS onset who reported using an individual HS was generally similar. The most commonly used HS in patients after MS was evening primrose oil (40.4%) followed by cranberry fruit extract (35.2%). There was no evidence for associations with progressive disease course or with choice of disease-modifying treatment. Dietary supplements are used more frequently by MS patients than controls. Use tends to increase after MS onset compared to before, especially for DS. The use of HS by MS patients is only modestly greater than by controls.

Genome-wide homozygosity and multiple sclerosis in Orkney and Shetland Islanders.
Three participants were removed on the basis of pedigree-genomic anomalies (n=263). Three measures of genome-wide homozygosity were generated for each individual, and association with MS was assessed using logistic regression models. No effect of genome-wide homozygosity was detected, indicating that inbreeding and consanguinity are not risk factors for MS in this population.

In conclusion, dysfunction of the neuroendocrine-immune system in patients with autoimmune diseases, including MS, seems to be important in the pathogenesis of these diseases. Increasing the knowledge of the neuroendocrine-immune system in MS can help to elucidate the underlying mechanisms of the inflammatory responses in MS and mutatis mutandis in other autoimmune diseases. Furthermore, intensive research on the modulatory function of the neuroendocrine-immune system may provide new therapeutic approaches for the treatment of MS in the near future.

Using regional homogeneity of resting-state fluctuations in the BOLD-signal as index of local functional connectivity, we show that local functional connectivity is impaired in the left cerebellum in MS. Regional homogeneity was found to be reduced in lobules V and VI of the left cerebellar hemisphere in patients with MS relative to controls. Further, patients with higher EDSS scores displayed less local connectivity in Crus I and dentate nucleus of left cerebellum. Similar trends were present in homologous regions of the right cerebellum. Post-hoc analyses showed that patients with higher lesion load of the left cerebellar peduncle showed more reduced local cerebellar connectivity.

Two meta-analyses of previously published fMRI studies investigating attention and working memory were conducted for MS patients and healthy controls, respectively. Resulting maps were contrasted to compare brain activation in patients and healthy controls. Significantly increased brain activation in the inferior parietal lobule and the dorsolateral prefrontal cortex was detected for healthy controls. In contrast, higher neuronal activation in MS patients was obtained in the left ventrolateral prefrontal cortex and the right premotor area. With this meta-analytic approach previous results of investigations examining cognitive function using fMRI are summarized and compared. Therefore a more general view on cognitive dysfunction in this heterogeneous disease is enabled.

Our results emphasize the importance of BBB pathology in MS, which we find to be most prominent in the periventricular NAWM, an area prone to development of MS lesions. Both the facts that recent relapse appears to cause widespread BBB disruption and that immunomodulatory treatment seems to attenuate this effect indicate that BBB permeability is intricately linked to the presence of MS relapse activity. This may reveal further insights into the pathophysiology of MS.

Autonomic dysfunction in multiple sclerosis.
Reports about frequency of AD in MS patients vary notably between groups. Nevertheless its impact on quality of life is substantial but, unfortunately, often overlooked. The aim of this article is to present a concise review of various symptoms and signs of autonomic system dysfunction in MS.

Adherence to disease-modifying therapies and attitudes regarding disease in patients with multiple sclerosis.
The analysis of results included 299 patients. Among the patients 18.5% missed at least one medication dose in the past 28 days. Patients taking Avonex were significantly more adherent then patients on other DMTs (p=0.005). Our study showed a higher then expected adherence among Slovenian patients with MS (81.5%). Our research did not confirm the influence of side effects or patients' attitudes regarding illness and therapy on adherence. However we found unexpectedly high percentage (71.8%) of patients belief that psychological factors are involved in MS aetiology.

Neuroendocrine Immunoregulation in Multiple Sclerosis.
Here we provide an overview of the complex system of crosstalk between the neuroendocrine and immune system as well as reported dysfunctions involved in the pathogenesis of autoimmunity, including MS. Finally, possible strategies to intervene with the neuroendocrine-immune system for MS patient management will be discussed. Ultimately, a better understanding of the interactions between the neuroendocrine system and the immune system can open up new therapeutic approaches for the treatment of MS as well as other autoimmune diseases.

Multiple sclerosis in pregnancy.
Preconceptual counseling to discuss the safety of medications in pregnancy, the antepartum period along with what the patient can expect during birth, and the postpartum period will be discussed.

Cognitive reserve in multiple sclerosis.
We review evidence that benefits of intellectual enrichment on cognitive status may stem from more efficient patterns of brain function. We discuss clinical implications and highlight important unanswered questions for future research on reserve against cognitive impairment in MS.

Defining and scoring response to IFN-β in multiple sclerosis.
In this Review, we focus on the many definitions of clinical response to IFN-β and explore the markers that can be used to predict this response. We also highlight advantages and limitations of the existing scoring systems in light of future expansion of these models to biological markers and to other classes of emerging therapies for MS.

Update on therapeutic options for multiple sclerosis.
The disorder has long been associated with clinical relapses and a disabling course. However, there has been a rapid expansion in the available treatment options for MS, and new insights into existing therapies, as decades of research has begun to produce tangible treatment results leading to newly approved an emerging therapies.

Entrapment syndrome of multiple nerves in graft-versus-host disease.
Electron microscopy demonstrated alterations of the myelin sheaths and marked depletion of normal-sized myelinated nerve fibers. Conclusions: In addition to polyneuropathy, chronic GVHD can be associated with peripheral nerve entrapment syndromes and should be added to the differential diagnosis of compressive neuropathies. Muscle Nerve 49: 138-142, 2014.

Multiple sclerosis: risk factors and their interactions.
these factors appear to act synergistically and the risk of MS in individuals exposed to more than one factor combines multiplicatively. Current evidence suggests that a large part of MS could be prevented and understanding how and when during life risk factors act will ultimately aid the development of prevention strategies.

Cerebral lesions of multiple sclerosis: is gadolinium always irreplaceable in assessing lesion activity?
The assessment of MS lesion activity should include a careful evaluation of T2-weighted images in addition to contrast enhancement assessment. The presence of an accompanying peripheral thin rim of hypointensity on T2-weighted images related best with contrast enhancement and subsequent lesion activity and may represent an additional pattern for disease activity assessment when gadolinium examination is contraindicated or influenced by prior therapy.

At least 13% of patients who fulfill the TMCWG criteria for definite and possible IATM will convert to MS. Functional recovery in IATM is poorer in patients with urinary sphincter dysfunction at admission or LETM on MRI.

We found a higher prevalence and incidence of Multiple Sclerosis among populations living in the eastern flank of Mount Etna. According to our data a possible role of TE cannot be ruled out as possible co-factor in the MS pathogenesis. However larger epidemiological study are needed to confirm this hypothesis.

Ethical challenges in paediatric clinical trials in multiple sclerosis.
Future treatment trials in children and adolescents with MS will require a multicentre design, definition and selection of key outcome measures, and identification of the most promising therapies. Risks versus benefits of each specific treatment should be weighed and comprehensively discussed.

Vitamin D levels in Hispanics with multiple sclerosis.
We found that the relationship between vitamin D and MS differs by Hispanic ethnicity. Hypovitaminosis D was significantly more common among Hispanics than among whites with MS, and the majority of Hispanics were vitamin D insufficient. Interestingly, there was no association between vitamin D levels and season or increasing disability in the Hispanics. Our findings imply that factors influencing vitamin D levels and possibly vitamin D requirements may vary by ethnicity in patients with MS. These results should be confirmed in larger, prospective multi-ethnic cohort studies.

Bruxism and temporal bone hypermobility in patients with multiple sclerosis.
The increase in magnitude of bi-temporal bone intracranial expansion was approximately six times greater in subjects with MS compared to controls. Therefore, jaw clenching/bruxism is associated with more marked displacement of the temporal bones and expansion of the cranial cavity in patients with MS than in control subjects.

Abnormal blood-brain barrier permeability in normal appearing white matter in multiple sclerosis investigated by MRI.
Our results emphasize the importance of BBB pathology in MS, which we find to be most prominent in the periventricular NAWM, an area prone to development of MS lesions. Both the facts that recent relapse appears to cause widespread BBB disruption and that immunomodulatory treatment seems to attenuate this effect indicate that BBB permeability is intricately linked to the presence of MS relapse activity. This may reveal further insights into the pathophysiology of MS.

Multiple sclerosis impairs regional functional connectivity in the cerebellum.
In patients, two clusters in the left posterior cerebellum expressed a reduction in regional homogeneity with increasing global disability as reflected by the Expanded Disability Status Scale (EDSS) score or higher ataxia scores. The two clusters were mainly located in Crus I and extended into Crus II and the dentate nucleus but with little spatial overlap. These findings suggest a link between impaired regional integration in the cerebellum and general disability and ataxia.

[Multiple sclerosis and familial Mediterranean fever: a case report].
Neurological complications of FMF are rare. It is important to rule out a neuro-Behçet disease in a FMF patient with neurological disorders. Previous studies and case reports on the association between FMF and MS have failed to draw a clear conclusion as to whether this is a true association or a simple coincidence. In our patient's clinical situation, we found no argument for changing the treatment of MS and FMF.

[Approaches to segment multiple-sclerosis lesions on conventional brain MRI].
Different sets of criteria are currently used for the diagnosis of multiple sclerosis (MS). Some are based on clinical features, while others are related to imaging findings. Among the image processing systems, specific criteria include spatial dissemination of lesions in one image or their temporal dissemination in images acquired at different time points. In addition, the evolution of the lesion load can be used to evaluate treatment efficiency in MS clinical research. Consequently, obtaining a precise segmentation of the MS lesion appears to be crucial. In the literature, a number of semi-automated or completely automated approaches have been proposed enabling a reduction of the inter- and intra-expert variability for manual delineations. A comprehensive state-of-the-art classification of the most representative systems is presented here.

[Choice of early and escalation treatment options for multiple sclerosis].
Here we summarize available data from studies on early treatment with immunomodulatory drugs for a first demyelinating event, also referred to as clinically isolated syndrome. Furthermore, options for the escalation of immunomodulatory therapy will be discussed, e.g. with the recently licensed monoclonal antibody natalizumab.

Cognitive impairment in multiple sclerosis.
It is only through further studies that it will be possible to identify patients with, or at risk of, cognitive impairment and to provide appropriate therapy to limit the effects of this potentially devastating symptom.

Differential diagnosis of suspected multiple sclerosis: a consensus approach.
Differential diagnosis leading to MS or alternatives is complex and a strong evidence base is lacking. Consensus-determined guidelines provide a practical path for diagnosis and will be useful for the non-MS specialist neurologist. Recommendations are made for future research to validate and support these guidelines. Guidance on the differential diagnosis process when MS is under consideration will enhance diagnostic accuracy and precision.

Development of autoimmune hepatitis type 1 after pulsed methylprednisolone therapy for multiple sclerosis: a case report.
A 43-year-old woman with multiple sclerosis (MS) was treated with pulsed methylprednisolone and interferon beta at a hospital. Four weeks after initiating treatment, liver dysfunction occurred and she was referred and admitted to our hospital. Clinical and laboratory findings were consistent with and fulfilled the criteria for drug-induced hepatitis, but not for autoimmune hepatitis (AIH). She was successfully treated with corticosteroids. As ataxia developed after 1 year, she was treated with pulsed methylprednisolone for 3 d, then readmitted to our hospital when liver dysfunction occurred. Clinical and laboratory findings led to the diagnosis of AIH. To the best of our knowledge, this is the second case of AIH developed after pulsed methylprednisolone for MS.

[Acute disseminated encephalomyelitis: study of factors involved in a possible development towards multiple sclerosis].
Some clinical and paraclinical patterns are considered to confer risk of developing MS when present in ADEM patients. Our study has aimed to: a) describe a series of 29 patients (22 children and 9 adults) admitted in our hospital and diagnosed of ADEM between 1990 and 2005; b) study those patients considered to have risk patterns of developing MS, and c) compare the child and adult populations of our series. After a median 55 month follow-up, 6 children (27%) and no adults developed MS. In our series, risk patterns for developing MS predicted conversion to MS more accurately in children than in adults. Eight patients (6 children and 2 adults) had sequelae, cognitive in 6 of them. Our work supports that also observed in recent publications: that both conversion to MS or presence of sequelae after an episode of ADEM are more frequent than traditionally considered.

[Antibodies to native and denatured DNA in multiple sclerosis].
The higher levels of antibodies were found in patients with remitting MS compared to primarily- and secondary progressive MS. The results obtained support the hypothesis that anti-DNA antibodies to DNA are the key component of the pathogenesis and their level depends on the immunoreactivity of the patient and MS course.

B cell-derived IL-15 enhances CD8 T cell cytotoxicity and is increased in multiple sclerosis patients.
Exposure of CD8 T cells to this cytokine enhanced their ability to kill glial cells as well as to migrate across an in vitro inflamed human blood-brain barrier. The elevated levels of IL-15 in patients relative to controls, the greater susceptibility of CD8 T cells from patients to IL-15, in addition to the enhanced cytotoxic responses by IL-15-exposed CD8 T cells, stresses the potential of therapeutic strategies to reduce peripheral sources of IL-15 in MS.

Morphostructural MRI abnormalities related to neuropsychiatric disorders associated to multiple sclerosis.
It is conceivable that grey matter pathology (i.e., global and regional atrophy, cortical lesions), which occurs early in the course of disease, may involve several areas including the dorsolateral prefrontal cortex, the orbitofrontal cortex, and the anterior cingulate cortex whose disruption is currently thought to explain late-life depression. Further MRI studies are necessary to better elucidate OCD pathogenesis in MS.

Disease-specific molecular events in cortical multiple sclerosis lesions.
we confirmed by immunohistochemistry that oxidative damage in cortical multiple sclerosis lesions is associated with oligodendrocyte and neuronal injury, the latter also affecting axons and dendrites. Our study provides new insights into the complex mechanisms of neurodegeneration and regeneration in the cortex of patients with multiple sclerosis.

Extracellular matrix metalloproteinase inducer shows active perivascular cuffs in multiple sclerosis.
In summary, we describe the prominence of extracellular matrix metalloproteinase inducer in central nervous system inflammatory perivascular cuffs, emphasize its dual role in matrix metalloproteinase induction and leucocyte adhesion, and highlight the elevation of extracellular matrix metalloproteinase inducer as an orchestrator of the infiltration of leucocytes into the central nervous system parenchyma.

Demyelinating disease in SLE: Is it multiple sclerosis or lupus?
This review discusses clinical, pathophysiological, radiological and therapeutic concepts of demyelinating disease of the CNS in SLE, focussing on its differentiation from MS and its relation with other CNS demyelinating processes, such as transverse myelitis, optic neuritis and neuromyelitis optica.

Can we switch microglia's phenotype to foster neuroprotection? Focus on multiple sclerosis.
While activated microglia have been observed in many neurological diseases of diverse etiology, "activation" indeed does not reveal the functional state of the cells which are often engaged in highly different roles. Indeed, microglia can play both detrimental and beneficial roles depending on inputs and feedback signals arising from the neural environment; such paradoxical roles are associated with phenotypes that range from so-called "classically activated", with highly pro-inflammatory features, to "alternatively activated" associated with a repair-oriented profile.

Predictors of successful acceptance of home telemanagement in veterans with Multiple Sclerosis.
The feasibility of the MS HAT system was assessed by (1) analyzing attitudinal surveys of veterans with MS who used the MS HAT system at home for over a month; (2) identifying factors affecting acceptance of the MS HAT system; (3) reviewing adherence of MS HAT users to self-testing regimen; (4) analyzing veteran feedback on MS HAT functionality using semi-structured qualitative interviews.

Monitoring technology for wheelchair users with advanced multiple sclerosis.
The sensors collect information related to the main issues of MS patients: fatigue, heat sensitivity and low mobility. Preliminary results show the signals as the wheelchair is moving, stopped and tilting. The system is able to capture sufficient relevant information to provide suggestions and alarms in a future stage. The system will be tested at The Boston Home, a specialized residence for adults with advanced MS.

A regenerative approach to the treatment of multiple sclerosis.
Evidence from a cuprizone-induced model of demyelination, in vitro and in vivo T-cell assays and EAE adoptive transfer experiments indicated that the observed efficacy of this drug results directly from an enhancement of remyelination rather than immune suppression. Pharmacological studies indicate that benztropine functions by a mechanism that involves direct antagonism of M1 and/or M3 muscarinic receptors. These studies should facilitate the development of effective new therapies for the treatment of multiple sclerosis that complement established immunosuppressive approaches.

Predictors and dynamics of postpartum relapses in women with multiple sclerosis.
Results confirm a favourable effect on relapses as pregnancy proceeds, and an early postpartum peak. Pre-conception DMT exposure and low ARR were independently protective against postpartum relapse. This novel finding could provide clinicians with a strategy to minimise postpartum relapse risk in women with MS planning pregnancy.

Systematic Review of Occupational Therapy-Related Interventions for People With Multiple Sclerosis: Part 2. Impairment.
art 1 (Yu & Mathiowetz, 2014) reviewed evidence for the effectiveness of activity- and participation-based interventions for people with MS. In contrast to the top-down approach, enabling occupational performance can be achieved through remediating impaired personal abilities. Therefore, Part 2 focuses on occupational therapy interventions targeting impairment. Studies included in this review focused on improving client factors and performance skills in people with MS, including cognition, emotional regulation, and motor and praxis skills.

Intrathecal baclofen in multiple sclerosis: too little, too late?
Delivery of ITB therapy requires expertly trained staff and proper facilities for pump management. This article summarizes the findings and recommendations of an expert panel on the use of ITB therapy in the MS population and the role of the physician and comprehensive care team in patient selection, screening, and management.

Aggregation of multiple sclerosis genetic risk variants in multiple and single case families.
The primary interest in the MSGB concept resides in its capacity to integrate cumulative genetic contributions to MS risk. This analysis underlines the high variability of family load with known common variants. This novel approach can be extended to other genetically complex diseases. Despite the emphasis on assembling large case-control datasets, multigenerational, multiaffected families remain an invaluable resource for advancing the understanding of the genetic architecture of complex traits.

Neuroimaging in multiple sclerosis: neurotherapeutic implications.
Advancements that hold promise for the future include new techniques that are sensitive to diffuse changes, the increased use of higher field scanners, measures that capture disease related changes in gray matter, and the use of combined structural and functional imaging approaches to assess the complex and evolving disease process that occurs during the course of MS.

Pregnancy in multiple sclerosis: clinical and self-report scales.
A concomitant improvement in the SF36 domains vitality (p < 0.001) and general health (p = 0.001) was found in patients. At the final visit, at least 9 months after delivery, no worsening of EDSS, GNDS, MSIS-29 or SF36 was observed compared with the (for MS, beneficial) third trimester. Duration of disease, relapses in the year preceding pregnancy or relapses during pregnancy were not associated with postpartum relapse. QoL is improved during pregnancy. Although relapse rate was increased directly after delivery, in the mid long term after delivery no adverse effects of pregnancy on MS were found.

Promoting return of function in multiple sclerosis: An integrated approach.
Most of the currently available disease modifying agents proved to be very effective in managing the relapse rate, however progressive neuronal damage continues to occur and leads to progressive accumulation of irreversible disability. For this reason, any therapeutic strategy aimed at restoration of function must take into account not only immunomodulation, but also axonal protection and new myelin formation. We further highlight the importance of an holistic approach, which considers the variability of therapeutic responsiveness as the result of the interplay between genetic differences and the epigenome, which is in turn affected by gender, age and differences in life style including diet, exercise, smoking and social interaction.

Thalamo-striato-cortical determinants to fatigue in multiple sclerosis.
The findings of the present study indicate that the thalamo-striato-cortical network is involved in the pathophysiology of fatigue in MS, and provide support for the theory of central fatigue. However, due to the limited number of participants and the somewhat heterogeneous sample of MS participants, these results have to be regarded as tentative, though they might serve as a basis for future studies.

Insights into the Mechanisms of the Therapeutic Efficacy of Alemtuzumab in Multiple Sclerosis.
several lines of evidence suggest that the long-term clinical effects of alemtuzumab are attributable to qualitative changes in repopulating lymphocyte subsets potentially leading to a rebalancing of the immune system. Here, we review the contribution of data from animal models, ex vivo human studies, and clinical trials to the understanding of the mechanisms underlying the therapeutic effect of alemtuzumab in patients with RRMS.

Outcome Measures for Individuals With Multiple Sclerosis: Recommendations From the American Physical Therapy Association Neurology Section Task Force.
The MSTF reviewed 63 OMs. A modified Delphi process was used to build consensus on recommendations for PWMS across the disability spectrum and in various health care settings. Nearly half of the OMs received ratings of 3 or 4 (Recommended or Highly Recommended, respectively) for use in in-patient rehabilitation and outpatient settings, and three of four MS- related disability groupings. The MSTF concluded that the recommendations have broad applicability for clinicians working with PWMS across the disability spectrum, in any health care setting. The recommendations can assist with making sound decisions when selecting OMs for PWMS.

Daclizumab for relapsing remitting multiple sclerosis.
There was no increased number of patients in any adverse events (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.89 to 1.07) or serious adverse events in daclizumab groups compared with placebo (RR 1.15, 95% CI 0.29 to 4.54). Infections were the most frequent adverse events in treated participants and were resolved with standard therapies. One trial was still ongoing.

Discovery of novel disease-specific and membrane-associated markers in a mouse model of multiple sclerosis.
These data provide a unique mechanistic insight into the dynamics of peripheral immune cell infiltration into CNS-privileged sites at a molecular level and has identified several candidate markers which represent promising targets for future multiple sclerosis therapies. The mass spectrometry proteomics data associated with this manuscript have been deposited to the ProteomeXchange Consortium with the dataset identifier PXD000255.

Sleep disorders in multiple sclerosis and their relationship to fatigue.
Nocturia may impact MS-related fatigue and should be considered. The treatment of underlying SD led to an improvement of MS-related fatigue. From a scientific point of view, SD should be examined in all studies investigating MS-related fatigue and be considered as a relevant confounder.

Functional magnetic resonance imaging of working memory among multiple sclerosis patients.
Normal performance of a challenging VWM task among high-functioning MS patients is associated with a shift toward greater activity in regions related to sensorimotor functions and anterior attentional/executive components of the VWM system. Posterior memory storage systems appeared unaffected, while portions of the visual processing and subvocal rehearsal systems were less active. Although a shift in neural activity was noted relative to HC participants, deviation from regions normally involved in VWM function was not observed in this patient sample.

Escalation to natalizumab or switching among immunomodulators in relapsing multiple sclerosis.
To evaluate whether an escalation approach was more effective in suppressing clinical and magnetic resonance imaging (MRI) activity than switching among immunomodulators in relapsing-remitting multiple sclerosis (RRMS) patients. We suggest that an escalation to natalizumab is more effective than switching among immunomodulators in RRMS patients who failed a first-line treatment.

Redox regulation of cellular stress response in multiple sclerosis.
Our data strongly support a pivotal role for redox homeostasis disruption in the pathogenesis of MS and, consistently with the notion that new therapies that prevent neurodegeneration through nonimmunomodulatory mechanisms can have a tremendous potential to work synergistically with current MS therapies, unravel important targets for new cytoprotective strategies.

Pulse pressure is associated with walking impairment in multiple sclerosis.
There was no association between any PP measure and 6 MW distance in controls (p>0.05 for all). In conclusion, PP is a predictor of gait performance in persons with MS. These findings suggest that vascular senescence and altered ventricular-vascular coupling may contribute, in part, to the deterioration of physical function in persons with MS.

Diffusion tensor imaging and cognitive speed in children with multiple sclerosis.
To compare white matter (WM) integrity in children with MS and healthy children using diffusion tensor imaging (DTI), and correlate DTI findings with disease activity, lesion burden, and cognitive processing speed. MS participants displayed lower FA values in the genu (p<0.005), splenium (p<0.001) and in NAWM of bilateral parietal, temporal, and occipital lobes (p<0.001) versus controls. FA and MD in the thalamus did not differ between groups. Higher lesion volumes correlated with reduced FA in CC and hemispheric NAWM. DTI metrics did not correlate with EDSS. FA values in CC regions correlated with Visual Matching (p<0.001) and SDMT (p<0.005) in MS participants only.

Extra-cranial venous flow in patients with multiple sclerosis.
We found no evidence to suggest that MS patients have excess of CCSVI. In addition we failed to observe a typical venous flow pattern in MS patients. Until carefully designed controlled studies to investigate CCVSI have been completed, invasive and potentially dangerous endovascular procedures as therapy for MS should be discouraged.

Sleep disturbances in multiple sclerosis.
Sleep disturbances are more common in MS patients than in the general population and limit these patients' quality of life. Therefore, we believe that these disturbances should be a focal point in any multidisciplinary treatment for MS.

Emerging injectable therapies for multiple sclerosis.
Ofatumumab is a monoclonal antibody that has shown efficacy in a small phase 2 trial. Animal models suggest that anti-LINGO1 antibody has remyelinating potential, and phase 2 trials of the antibody are underway. Further clarification of purported mechanisms of action and continued surveillance will be essential to establish the safety and clinical efficacy of these drugs in patients with relapsing-remitting MS.

Preference-based Health status in a German outpatient cohort with multiple sclerosis.
MS considerably impairs patients' health status. Guidelines aiming to improve self-reported health status should include treatment options for depression and fatigue. Physicians should be aware of depression and fatigue as co-morbidities. Future studies should consider the minimal clinical difference when health status is a primary outcome.

[New and emerging treatments for multiple sclerosis].
A better knowledge of fundamental pathophysiology is associated with the development of new molecules targeting the immunological cascade of the disease as well as the mechanisms promoting remyelination and repair.

Quick screening of cognitive function in Indian multiple sclerosis patients using Montreal cognitive assessment test-short version.
Cognitive impairments in multiple sclerosis (MS) are now well recognized worldwide, but unfortunately this domain has been less explored in India due to many undermining factors. The aim of this study was to evaluate cognitive impairments in Indian MS patients with visual or upper limb motor problems with the help of short version of Montreal cognitive assessment test (MoCA).
The 12 points, short version of MoCA, is a useful brief screening tool for quick and early detection of mild cognitive impairments in subjects with MS. It can be administered to patients having visual and motor problems. It is of potential use by primary care physicians, nurses, and other allied health professionals who need a quick screening test. No formal training for administration is required. Financial and time constraints should not limit the use of the proposed instrument.

Interleukin 2 receptor α chain gene polymorphisms and risks of multiple sclerosis and neuromyelitis optica in southern Japanese.
Interleukin 2 receptor α subunit (IL2RA) is a genetic risk for multiple sclerosis (MS) in Caucasians. However, the association between MS and IL2RA in Japanese idiopathic demyelinating diseases of the central nervous system has not been examined. Although the possibility that IL2RA is a risk factor for MS development was not confirmed in this Japanese population, IL2RA gene polymorphisms were able to modify the disease activity in female MS patients, but had no influence on either susceptibility or disease phenotype in NMO/NMOSD patients.

Dilated Virchow-Robin spaces and multiple sclerosis: 3 T magnetic resonance study.
Our results confirm previous reports regarding the increase in VRSd in nonactive phases of MS and support the immunological role of the VRS within the central nervous system. The lack of correlation between VRSd and the degree of GCA and their prevailing localisation in atypical sites in MS patients make VRSd a potential marker of inflammatory-demyelinating disease.

Teriflunomide for the treatment of relapsing multiple sclerosis: a review of clinical data.
To review the pharmacology and clinical data for teriflunomide in relapsing multiple sclerosis (MS).
Teriflunomide is an effective and safe oral treatment option for relapsing MS. It can be used as monotherapy or added to an interferon or glatiramer acetate. It reduces the rate of relapse and may slow disease progression. The advantages of this drug are the convenience of oral administration and good tolerability. The disadvantage is the lack of long-term safety data and data about the benefit of combination therapy.

MicroRNAs and multiple sclerosis: from physiopathology toward therapy.
The miRNAs in central nervous system lesions and peripheral blood are potential biomarkers for diagnostic and prognostic use. Also, miRNA mimics, small-molecule inhibitors of specific miRNAs, and antisense oligonucleotides could be therapeutic weapons that facilitate us to combat the disease.

Multiple sclerosis and risk of Parkinson's disease: a Danish nationwide cohort study.
Case reports have observed a co-occurrence of multiple sclerosis (MS) and Parkinson's disease (PD) and it has been hypothesized that MS lesions could affect dopaminergic pathways causing parkinsonism. Our aim was to examine the association between MS and PD in a historically prospective cohort study using Danish nationwide register data. Our data do not suggest an increased risk of PD amongst patients with MS.

Incidence and prevalence of multiple sclerosis in the UK 1990-2010: a descriptive study in the General Practice Research Database.
To estimate the incidence and prevalence of multiple sclerosis (MS) by age and describe secular trends and geographic variations within the UK over the 20-year period between 1990 and 2010 and hence to provide updated information on the impact of MS throughout the UK.
We estimate that 126 669 people were living with MS in the UK in 2010 (203.4 per 100 000 population) and that 6003 new cases were diagnosed that year (9.64 per 100 000/year). There is an increasing population living longer with MS, which has important implications for resource allocation for MS in the UK.

Investigation of heterogeneity in the association between interferon beta and disability progression in multiple sclerosis: an observational study.
It was recently reported that there was no significant overall association between interferon beta exposure and disability progression in relapsing-remitting multiple sclerosis (RRMS) patients in an observational study from Canada. In the current study, the potential for heterogeneity in the association between exposure to interferon beta and disability progression across patients' baseline characteristics was investigated. RRMS patients with more frequent relapses at baseline may be more likely to benefit from interferon beta treatment with respect to long-term disability progression.

Multiple sclerosis in the mount etna region: possible role of volcanogenic trace elements.
To evaluate the possible association between Multiple Sclerosis and exposure to volcanogenic trace elements. We found a higher prevalence and incidence of Multiple Sclerosis among populations living in the eastern flank of Mount Etna. According to our data a possible role of TE cannot be ruled out as possible co-factor in the MS pathogenesis. However larger epidemiological study are needed to confirm this hypothesis.

Comparison of 3D Cube FLAIR with 2D FLAIR for Multiple Sclerosis Imaging at 3 Tesla.
The difference was mostly accounted for by supratentorial lesions (N = 372 vs. N = 216) while the infratentorial lesion counts were low in both sequences. SNRs and CNRs were significantly higher in CUBE FLAIR with the exception of the CNR of lesion to gray matter, which was not significantly different. Conclusion: Cube FLAIR showed a higher sensitivity for MS lesions compared to a 2 D FLAIR sequence. 3 D FLAIR might replace 2 D FLAIR sequences in MS imaging in the future.

Methylation differences at the HLA-DRB1 locus in CD4+ T-Cells are associated with multiple sclerosis.
To identify methylation changes associated with MS, we performed a genome-wide DNA methylation analysis of CD4+ T cells from 30 patients with relapsing-remitting MS and 28 healthy controls using Illumina 450K methylation arrays. Our findings provide the first evidence for association of DNA methylation at HLA-DRB1 in relation to MS risk. Further studies are now warranted to validate and understand how these findings are involved in MS pathology.

Cutaneous and pulmonary sarcoidosis following treatment of multiple sclerosis with interferon-beta-1b: a case report.
Sarcoidosis is considered one of the most common multiple sclerosis imitators with involvement of the central nervous system. However, although rare, sarcoidosis can develop following treatment with interferon-beta-1b and should be considered in patients with multiple sclerosis treated with beta-interferons who develop pulmonary or extra-pulmonary manifestations of sarcoidosis. Interferon-beta-1b discontinuation is the first and most important step in the treatment of such cases followed by treatment with corticosteroids.

Inflammation in neurodegenerative diseases - an update.
A better understanding of how immune responses are involved in neuronal damage and regeneration, as reviewed here, will be essential to develop effective therapies to improve quality of life, and mitigating the personal, economic and social impact of these diseases. This article is protected by copyright. All rights reserved.

Self-tolerance in multiple sclerosis.
Regulatory T cells suppress the general local immune response via bystander effects rather than through individual antigen-specific responses. Interestingly, the beneficial effects of currently approved immunomodulators (interferons β and glatiramer acetate) are associated with a restored regulatory T cell homeostasis. However, the feedback regulation between Th1 and Th17 effector cells and regulatory T cells is not so simple and tolerogenic mechanisms also involve other regulatory cells such as B cells, dendritic cells and CD56(bright) natural killer cells.

Increased determinism in brain electrical activity occurs in association with multiple sclerosis.
Increased determinism (decreased complexity) of brain electrical activity has been associated with some brain diseases. Our objective was to determine whether a similar association occurred for multiple sclerosis (MS). The mean±SD of %R for the MS subjects was 6·6±1·3%, compared with 5·1±1·3% in the normal group (P = 0·017), indicating that brain activity in the subjects with MS was less complex, as hypothesized. The groups were not distinguishable using %D or spectral analysis.

Multiple sclerosis and sexual dysfunction.
Maintaining a healthy sexual life with MS is an important priority. The treatment of SD requires multidisciplinary teamwork and cooperation among specialists, individual patients, partners and the society.

The symptom inventory disability-specific short forms for multiple sclerosis: reliability and factor structure.
To further the development of the 99-item Symptom Inventory (SI) for multiple sclerosis (MS) using modern test theory methods to create 3 disability-specific short forms for MS patient subgroups identified using Performance Scale (PS) items. This study provides empirical support for a 10-scale symptom measure for use in MS clinical research, with short forms in 5 scales tailored to have good specificity for people with mild, moderate, and severe disability and single forms for the remaining 5 scales. The PS items can serve as a screener for these disability-specific short forms, which provide choice and flexibility that are similar to a computerized adaptive test but without the reliance on real-time computer infrastructure.

Pharmacological treatment for memory disorder in multiple sclerosis.
We found no convincing evidence to support the efficacy of pharmacological symptomatic treatment for MS-associated memory disorder because most of available RCTs had a limited quality. Whether pharmacological treatment is effective for memory disorder in patients with MS remains inconclusive. However, there is moderate-quality evidence that donepezil 10 mg daily was not effective in improving memory in MS patients with mild memory impairment, but had a good tolerability. Adverse events such as nausea, diarrhoea and abnormal dreams were not frequent but were associated with treatment. Ginkgo biloba, memantine and rivastigmine were safe and well tolerated and no serious adverse effects were reported. Future large-scale RCTs with higher methodological quality are needed.

Risk acceptance in multiple sclerosis patients on natalizumab treatment.
We aimed to investigate the ability of natalizumab (NTZ)-treated patients to assume treatment-associated risks and the factors involved in such risk acceptance. Risk acceptance is a multifactorial phenomenon, which might be partly explained by an adaptive process, in light of the higher risk acceptance amongst NTZ-treated patients and, especially, amongst those who are JCV seropositive but still have low PML risk, but which seems also intimately related to personality traits.

Ten Years of Proteomics in Multiple Sclerosis.
In this review, we summarize these data, presenting their value to the current knowledge of the disease mechanisms, as well as their importance as identification of biomarkers or treatment targets.

Body fluid biomarkers in multiple sclerosis.
Despite the need for biomarkers and extensive research to identify them, validation and clinical application of biomarkers is still an unmet need in multiple sclerosis, and large gaps remain between exploratory biomarkers proposed in many studies, validated biomarkers, and biomarkers that are integrated into routine clinical practice.

Plasma homocysteine levels in patients with multiple sclerosis in the Greek population.
In recent years, there has been increasing interest in the role of plasma homocysteine (Hcy) as a possible risk factor for several diseases of the central nervous system. The aim of this study was to determine the plasma levels of Hcy in a group of multiple sclerosis (MS) patients from a Greek population and the possible correlation with age, disability status, activity or duration of disease, sex, and treatment. The preliminary data suggest that Hcy levels were not elevated in our sample of Greek MS patients, which does not support previous findings of a significant correlation between elevated serum Hcy levels and MS. Further studies to establish a possible association between MS and Hcy levels in the context of different ethnic groups with different habits are needed.

Predictors of changes in suicidality in multiple sclerosis over time.
Interventions aimed at evaluating and monitoring depression over time should be considered in order to reduce the risk of suicidality. Implications for Rehabilitation Due to the inconsistency and unpredictability of MS, depression should be assessed routinely. Given the high prevalence of depression and suicidality in MS, mental health services should be available and encouraged by healthcare providers treating individuals with MS.

Fumarates improve psoriasis and multiple sclerosis by inducing type II dendritic cells.
umarates improve multiple sclerosis (MS) and psoriasis, two diseases in which both IL-12 and IL-23 promote pathogenic T helper (Th) cell differentiation. However, both diseases show opposing responses to most established therapies. First, we show in humans that fumarate treatment induces IL-4-producing Th2 cells in vivo and generates type II dendritic cells (DCs) that produce IL-10 instead of IL-12 and IL-23. In mice, fumarates also generate type II DCs that induce IL-4-producing Th2 cells in vitro and in vivo and protect mice from experimental autoimmune encephalomyelitis.

Cesarean delivery may increase the risk of multiple sclerosis.
This study was designed to evaluate whether mode of delivery (vaginal versus cesarean section), as a perinatal factor, affects susceptibility to MS. Our results suggest that those born by vaginal delivery are at a lower risk of subsequent MS. These preliminary findings will need to be addressed in a much larger and preferably prospective study.

Fatigue and heat sensitivity in patients with multiple sclerosis.
Fatigue is one of the most common and troubling symptoms of multiple sclerosis (MS), and heat is often reported as a trigger. Although it is assumed that this heat sensitivity is specific for MS, the evidence for disease specificity is limited. We studied the relationship between fatigue, heat sensitivity, and environmental temperature, and its specificity for MS. Our findings support the assumption that heat sensitivity regarding fatigue has an MS-specific component. Although patients with MS experience a relationship between environmental temperature and fatigue, objective assessment by climatological data could not confirm this.

Patient satisfaction in rehabilitation of patients with multiple sclerosis.
The motor and non-motor symptoms of multiple sclerosis often result in a substantially reduced health-related quality of life. We surveyed patient satisfaction and own evaluation of the benefit of a period spent at a specialised rehabilitation centre. Patients who have had stays at the Hakadal MS rehabilitation centre are satisfied and feel that the stay will be of great importance to their level of functioning and mastery.

Caregiving in multiple sclerosis.
Rehabilitation medicine professionals should be aware of the high risk of caregiver burden. Assessment of caregiver needs and appropriate intervention will help minimize the burden on caregivers.

Exercise in multiple sclerosis.
General guidelines are available for exercise prescription for the MS population. There are several recommendations that may help improve the quality of future MS exercise trials.

Current evaluation of alemtuzumab in multiple sclerosis.
Alemtuzumab offers induction strategy for very active relapsing MS patients who have failed conventional therapy, and possibly selected treatment-naive patients. Alemtuzumab use is likely to be restricted to specialized MS centers, with long-term monitoring to determine the true risk for adverse effects.

Dimethyl Fumarate (Tecfidera): A New Oral Agent for Multiple Sclerosis.
To describe the clinical evidence supporting the safety, efficacy, and clinical utility of oral dimethyl fumarate for the treatment of multiple sclerosis (MS). In March 2013, dimethyl fumarate was approved as a third oral option for patients with relapsing forms of MS. Although no head-to-head trials have been conducted, a comparison of data from phase III trials suggests that the efficacy of dimethyl fumarate is comparable to that of existing oral agents and may offer a preferable safety profile.

Optic coherence tomography findings in relapsing-remitting multiple sclerosis patients of the northwest of Iran.
Optical coherence tomography (OCT) is a simple, high-resolution technique to quantify the thickness of retinal nerve fiber layer (RNFL) and macula volume, which provide an indirect measurement of axonal damage in multiple sclerosis (MS). This study aimed to evaluate OCT finding in relapsing-remitting MS patients of the northwest of Iran and compare them with a normal control group.
Findings of the present study in the northwest of Iran buttress the idea that RNFL thickness can be greatly affected by MS. Our results also indicate that this effect is associated with ON and MS duration and severity.

Clinical relevance and functional consequences of the TNFRSF1A multiple sclerosis locus.
We set out to characterize the clinical impact and functional consequences of rs1800693(G), the multiple sclerosis (MS) susceptibility allele found in the TNFRSF1A locus. The MS rs1800693(G) susceptibility allele affects the magnitude of monocyte responses to TNF-α stimulation, and the TNF pathway may be one network in which the effect of multiple MS genes becomes integrated.

Major depression and multiple sclerosis - a case report.
Existing therapies that target immune modulation are largely ineffective in halting the progression of the disease and are fraught with severe side effects. Therefore, managing the comorbidities of MS is of utmost importance for long-term patient care and quality of life.

Cognitive reserve and patient-reported outcomes in multiple sclerosis.
The present work investigates the relationship between cognitive reserve and demographic characteristics, health behaviors, and patient-reported outcomes (PROs). This expanded measurement of cognitive reserve captures both the passive and active aspects of the construct, and there is a consistent and substantial relationship with PROs. Individuals with high passive and/or active reserve are healthier and experience higher levels of well-being.

MP2RAGE multiple sclerosis magnetic resonance imaging at 3 T.
he results show that the 3D T1-weighted high-resolution MP2RAGE contrast provides a sensitive means for MS lesion assessment. The additional quantitative T1 relaxation time maps obtained with the MP2RAGE provide further potential diagnostic and prognostic information that could help (a) to better discriminate lesion subtypes and (b) to stage and predict the activity and the evolution of MS. Results also indicate that the T2-weighted double-inversion recovery and FLAIR-SPACE contrasts are attractive complements to the MP2RAGE for lesion detection.

Chronic cerebrospinal venous insufficiency and venous stenoses in multiple sclerosis.
The traditional view that multiple sclerosis (MS) is an autoimmune disease has recently been challenged by the claim that MS is caused by chronic cerebrospinal venous insufficiency (CCSVI). Although several studies have questioned this vascular theory, the CCSVI controversy is still ongoing. Our aim was to assess the prevalence of CCSVI in Danish MS patients using sonography and compare these findings with MRI measures of venous flow and morphology. Our results do not corroborate the presence of vascular pathology in RRMS and we found no evidence supporting the CCSVI hypothesis.

A patient with Leiden V mutation, multiple sclerosis, psoriasis, and sicca syndrome: could celecoxib and fingolimod adversely affect the heart?
The paper describes the case of a patient affected by a combination of genetic and autoimmune diseases (multiple sclerosis, psoriatic arthritis, Leiden V mutation, and sicca syndrome) and hypertension. The psoriatic arthritis was treated with celecoxib and multiple sclerosis with fingolimod. The patient developed high fever and endocarditis, resulting in severe mitral regurgitation, atrial fibrillation, and congestive heart failure. Evidence is suggestive of adverse effects of potent immunosuppressive and anti-inflammatory therapies with biologic agents and the cardiovascular system. Fingolimod increases susceptibility to infections and induced endocarditis resulting in severe mitral regurgitation, atrial fibrillation, and congestive heart failure. Managed care systems limit the contact among basic care physicians and specialists. However, the process by which the optimal decision may be reached for a patient with a complex pathology is shared decision making, where the risk of severe complications and medical expenses may be reduced.

Acute demyelinating lesions with restricted diffusion in multiple sclerosis.
It is widely accepted that typical acute demyelinating lesions in relapsing-remitting multiple sclerosis(RRMS) exhibit vasogenic edema with increased diffusion, as demonstrated by an increased apparent diffusion coefficient on MRI. In contrast, acute ischemic lesions demonstrate cytotoxic edema with restricted diffusion. Recent reports have documented selected cases of acute demyelinating lesions exhibiting restricted diffusion (ADLRD) in MS. We aimed to assess the morphologies, distributions, signal characteristics and changes over time of nine ADLRD. An additional goal was to obtain clinical correlations and relate our findings to all previously published case reports describing ADLRD. Our results and review of prior published cases suggest that ADLRD represent a new variant of MS lesion. The restricted diffusion that is a characteristic of ADLRD on MRI is a new challenge in the differential diagnosis of stroke in young adults. The pathogenesis of ADLRD remains to be understood.

Desirability and expectations of the UK MS Register: Views of people with MS.
This study elicited the views of people with Multiple Sclerosis (PwMS) on the desirability and expectations regarding a UK Register for MS. The security and accessibility of the website, the validity of the data, and mismatches between the expected and actual uses, are all issues of importance in the development of e-health tools, if PwMS are to be successfully engaged over time.

Healthcare provider beliefs about exercise and fatigue in people with multiple sclerosis.
Healthcare providers are encouraged to consider strategies of active listening and careful observation when providing individualized exercise programs for people with MS-related fatigue. In addition, recognition and understanding of the complex nature of fatigue by the interdisciplinary team might facilitate more positive exercise experiences for this population.

Autoantigens and autoantibodies in multiple sclerosis.
The overactive pro-inflammatory Th1 cells and clonal expansion of B cells initiate an inflammatory cascade with several cellular and molecular immune components participating in MS pathogenic mechanisms. In this scenario, autoantibodies and autoantigens have a significant role in immunopathogenesis, diagnosis and therapeutic targets of MS. In this review, we try to introduce the autoantigens and autoantibodies and explain their roles in pathogenesis of MS.

Chromosomal radiosensitivity in patients with multiple sclerosis.
Induced micronuclei yield was significantly lower in the irradiated samples from treated relapsing-remitting multiple sclerosis patients than in healthy controls and relapsing-remitting not treated patients. Intrinsic sensitivity of lymphocytes subpopulations to the apoptotic effect of immunomodulatory treatment could be responsible for this result.

Vitamin D and multiple sclerosis: where do we go from here?
Vitamin D as a treatment for MS is an emerging concept and both current and anticipated data will be covered. Lastly, we discuss future challenges, ideas on how to move from association to causation, and the prospect of primary prevention of this disabling disease.

Validation of patient determined disease steps (PDDS) scale scores in persons with multiple sclerosis.
The Patient Determined Disease Steps (PDDS) is a promising patient-reported outcome (PRO) of disability in multiple sclerosis (MS). To date, there is limited evidence regarding the validity of PDDS scores, despite its sound conceptual development and broad inclusion in MS research.This study examined the validity of the PDDS based on (1) the association with Expanded Disability Status Scale (EDSS) scores and (2) the pattern of associations between PDDS and EDSS scores with Functional System (FS) scores as well as ambulatory and other outcomes. This study provides novel evidence supporting the PDDS as valid PRO of disability in MS.

Effect of 4-aminopyridine on vision in multiple sclerosis patients with optic neuropathy.
The objective of this randomized, double-blind, placebo-controlled, crossover study was to examine if patients with optic neuropathy would derive a therapeutic benefit from 4-aminopyridine (4-AP) treatment. Furthermore, the study was intended to determine if patients with certain P100 latencies or retinal nerve fiber layer (RNFL) measures would be more likely to respond to therapy.
4-Aminopyridine is useful for improving vision in patients with demyelinating optic neuropathy. Future clinical trials may be able to enrich a patient population for potential responders using OCT and VEP measures. Selecting patients for future trials should use RNFL measures as part of inclusion/exclusion criteria.

Cortisol awakening response is linked to disease course and progression in multiple sclerosis.
Dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis has frequently been reported in multiple sclerosis (MS). So far, HPA axis function in MS has predominantly been studied under pharmacological stimulation which is associated with a series of methodological caveats. Knowledge of circadian cortisol patterns and cortisol awakening response (CAR) is still limited.
Circadian cortisol release, in particular CAR, shows a course specific pattern with most pronounced release in RRMS. There is also some evidence for greater CAR in RRMS patients with EDSS progression. As a consequence, CAR might be of predictive value in terms of neurological disability in RRMS patients. The possible role of neuroendocrine-immune interactions in MS pathogenesis is further discussed.

Functional connectivity changes within specific networks parallel the clinical evolution of multiple sclerosis.
In multiple sclerosis (MS), the location of focal lesions does not always correlate with clinical symptoms, suggesting disconnection as a major pathophysiological mechanism. Resting-state (RS) functional magnetic resonance imaging (fMRI) is believed to reflect brain functional connectivity (FC) within specific neuronal networks. FC changes seem to parallel patients' clinical state and capability of compensating for the severity of clinical/cognitive disabilities.

Novel therapeutic options for multiple sclerosis.
Half a dozen immunomodulators with proven efficacy in RRMS are now undergoing evaluation in Phase III trials in the CPMS indication. Neuroprotective drugs that prevent demyelination and/or improve remyelination would be interesting for CPMS, but these drugs are currently in the early development phase and their efficacy has not been demonstrated yet.

Iron depletion induced by bloodletting and followed by rhEPO administration as a therapeutic strategy in progressive multiple sclerosis: A pilot, open-label study with neurophysiological measurements.
To evaluate the concept that iron depletion (ID) induced by bloodletting and followed by recombinant human erythropoietin (rhEPO) administration could be a therapeutic strategy in progressive multiple sclerosis (PMS) and that it could be assessed by neurophysiological measurements. The combined ID-rhEPO therapy could authorize a prolonged administration of rhEPO in PMS patients, able to modify cortical excitability of the glutamatergic and gabaergic circuits. These preliminary data are encouraging to design a larger, controlled therapeutical trial to assess the value of such a strategy to improve functional symptoms in PMS patients, and maybe to prevent axonal degeneration. Neurophysiological measurements based on cortical excitability studies could provide sensitive parameters to evaluate treatment-induced changes in this context.

Evoked potentials in multiple sclerosis.
This article is a brief overview of additional ways in which central nervous system (CNS) physiology-as measured by EPs-can still contribute value in the management of MS in the era of MRIs.

Management of Relapsing-Remitting Multiple Sclerosis [Internet].
The emergence of novel oral and injectable agents necessitates consideration of their place in therapy, including the potential for combination therapy. Thus, the comparative clinical and cost-effectiveness of currently available and emerging disease-modifying agents for RRMS, both alone and in combination, need to be determined.

Objective duplex ultrasound evaluation of the extracranial circulation in multiple sclerosis patients undergoing venoplasty of internal jugular vein stenoses: A pilot study.
Chronic cerebrospinal venous insufficiency (CCSVI) is a condition associated with multiple sclerosis (MS) and manifested by stenoses in the extracranial venous circulation. There is a need for an objective non-invasive assessment of CCSVI that is able to accurately identify the location of stenoses and quantify physiological changes in blood flows following treatment.
The ECDU examination described provides a reliable objective assessment of IJV and VV stenoses and, with the use of BVFs, can quantify the degree of obstruction. These results support the use of ECDU as a non-invasive post-operative assessment of the success of venoplasty. The ability of ECDU to measure GACBF provides an additional parameter to monitor vascular pathophysiology in MS patients. The current findings support the view that the early symptomatic benefits observed after venoplasty for stenoses in the extracranial venous circulation may be the result of increased cerebral perfusion.

Characterizing contrast-enhancing and re-enhancing lesions in multiple sclerosis.
In multiple sclerosis (MS), contrast-enhancing lesions (CELs) in T1-weighted postcontrast MRI are considered markers of blood-brain barrier breakdown. It remains unknown if re-enhancement can be considered a radiologic indicator of different pathology in CELs. We investigated 1) the incidence of re-enhancing lesions (re-CELs) from chronic lesions; 2) differences in size, magnetization transfer ratio (MTR), and likelihood to appear as acute black holes (aBHs) between new lesions (n-CELs) and re-CELs; and 3) associations between re-CELs and features indicating more advanced disease.
Nearly 20% of CELs represent the reoccurrence of enhancement in chronic plaques. Re-CELs represent larger areas of inflammation, not necessarily associated with larger areas of edema.

Microcystic macular oedema in multiple sclerosis is associated with disease severity.
Microcystic macular oedema may also contribute to visual dysfunction beyond that explained by nerve fibre layer loss. Microcystic changes need to be assessed, and potentially adjusted for, in clinical trials that evaluate macular volume as a marker of retinal ganglion cell survival. These findings also have implications for clinical monitoring in patients with multiple sclerosis on sphingosine 1-phosphate receptor modulating agents.

Biplanar MRI for the assessment of the spinal cord in multiple sclerosis.
To investigate the entire spinal cord (SC) of multiple sclerosis (MS) patients with biplanar MRI and to relate these MRI findings to clinical functional scores. Biplanar MRI facilitates a comprehensive identification, localization, and grading of pathological SC findings in MS patients. This improves the confidence and utility of SC imaging.

Periventricular demyelination and axonal pathology is associated with subependymal virus spread in a murine model for multiple sclerosis.
Theiler's murine encephalomyelitis virus (TMEV) infection of mice is a widely used animal model for demyelinating disorders, such as multiple sclerosis (MS). The aim of the present study was to identify topographical differences of TMEV spread and demyelination in the brain of experimentally infected susceptible SJL/J mice and resistant C57BL/6 mice. Summarized, the demonstration of ependymal infection and subjacent spread into the brain parenchyma as well as regional virus clearance despite ongoing demyelination and axonal damage in other CNS compartments allows new insights into TME pathogenesis. This novel aspect of TMEV CNS interaction will enhance the understanding of region-specific susceptibilities to injury and regenerative capacities of the brain in this MS model.

Immunoadsorption therapy in patients with multiple sclerosis with steroid-refractory optical neuritis.
In multiple sclerosis relapses refractory to intravenous corticosteroid therapy, plasma exchange is recommended. Immunoadsorption (IA) is regarded as an alternative therapy, but its efficacy and putative mechanism of action still needs to be established. IA was effective in the treatment of corticosteroid-refractory optic neuritis. IA influenced the humoral immune response. Strikingly, however, we found strong evidence that demyelination products and immunological mediators were also cleared from plasma by IA.

Faith as a Resource in Patients with Multiple Sclerosis Is Associated with a Positive Interpretation of Illness and Experience of Gratitude/Awe.
The aim of this cross-sectional anonymous survey with standardized questionnaires was to investigate which resources to cope were used by patients with multiple sclerosis (MS). We focussed on patients' conviction that their faith might be a strong hold in difficult times and on their engagement in different forms of spirituality. The ability to reflect on what is essential in life, to appreciate and value life, and also the conviction that illness may have meaning and could be regarded as a chance for development was low in R-S- individuals which either may have no specific interest or are less willing to reflect these issues.

Evolution of Quality of Life in Renal Transplant Recipients and Patients With Multiple Sclerosis: A Follow-up Study.
We aimed to compare the evolution of quality of life in 2 medical conditions under immunotherapy (cadaveric renal transplantation [G1] and multiple sclerosis [G2]), and to assess the clinical significance of the results compared with a representative age-adjusted sample of the general Spanish population (G3). Renal transplant recipients need specialized health care 1 year after transplantation because they still display relevant impairment in daily functioning compared with the general population.

Future directions of multiple sclerosis rehabilitation research.
he conference was presented by the University of Washington's Multiple Sclerosis Rehabilitation Research and Training Center and focused on the current state of research into secondary conditions, outcomes measurement, employment, and the utility of psychotherapeutic interventions. This article discusses the details and recommendations of this conference.

Visual issues in multiple sclerosis.Multiple sclerosis has several ophthalmic manifestations, including optic neuritis, internuclear ophthalmoplegia, and nystagmus. The presentation, treatment, and prognosis of visual complaints secondary to multiple sclerosis are discussed. Additionally, the use of optical coherence tomography and complications related to the use of fingolimod are considered.

Multiple Sclerosis and Fatigue: Understanding the Patient's Needs.
(1) To assess, from the perspective of individuals living with MS, the relevance of a subset of items from the PROMIS fatigue item bank. (2) To identify additional aspects of fatigue that individuals with MS believe are important for clinicians when asking about their fatigue experience.

Movement disorders in multiple sclerosis.
This article reviews terminology used to describe movement disorders, discusses individual movement disorders and their occurrence in patients with multiple sclerosis, and reviews treatment options.

BCG vaccine for clinically isolated syndrome and MS: Infections and protective immunity.
Can infections ever be beneficial for MS? The long-held yet unproven "hygiene hypothesis" proposes that certain infections early in life might reduce the risk of developing autoimmune diseases by inducing protective immunity.2 In addition, parasitic intestinal infections in people with MS may reduce disease activity.3 It follows that better sanitation and common use of disinfectants and antibiotics may account in part for the increased prevalence of MS and other autoimmune diseases in North America and much of Europe, compared with Africa, South America, and parts of Asia. If true, might we harness this natural phenomenon to develop new treatments for MS?

Can we optimize our teams? Multidisciplinary care for multiple sclerosis.
Using a multidisciplinary approach, the Auvergne MS network has explored other avenues of domiciliary-based care to seek improvements in the patient-centered management of MS. These include: access to high-dose methylprednisolone in the home, ensuring appropriate supervision and support; participation in national clinical research programs coordinated from hospital centers of excellence; provision of multidisciplinary clinic services where healthcare professionals across different disciplines can attend to the patient on the same day in the same center of care; development of individual and group-based cognitive therapy programs; educational programs focusing on the management of fatigue and cognitive impairment associated with MS; and educational programs focusing on optimal use of immunomodulating agents in MS patients.

Measuring symptoms and wellness in the multiple sclerosis patient: issues in measurement.
This review examines some important basic principles of measurement and considers issues as they apply to examples of measures used for patients with multisymptomatic illnesses such as multiple sclerosis, with a particular focus on application of the spasticity 0-10 Numerical Rating Scale and its correlation with the Patient Global Impression of Change scale.

Environmental factors in multiple sclerosis.
If confirmed, these findings suggest that a high proportion of MS cases could be effectively prevented by vitamin D supplementation. Furthermore, there is growing evidence that vitamin D insufficiency is a risk factor for conversion from clinically isolated syndrome to MS and for MS progression. Both prevention and treatment trials with vitamin D are needed to confirm these findings and to determine optimal levels of vitamin D.

To establish a detailed technical procedure for studying the anatomical correlates of chronic cerebrospinal venous insufficiency in cadavers of multiple sclerosis and control subjects, and to present our findings of the normal anatomic venous structures, with reference to previous descriptions from the literature. Post-mortem studies can provide valuable information about the architecture of intraluminal structures. In addition to providing a more thorough understanding of the extracranial venous system, we hope that our discussion and technical approach to dissection will help with future gross anatomical inspection of CCSVI.

In this study of 1181 MS patients and 1886 controls we found that Bout Onset MS was associated with the C-allele of the marker rs391745 near the HERV-Fc1 locus (p=0.003), while primary progressive disease was not. The ability to see genetic differences between subtypes of MS near this gene speaks for the involvement of the virus HERV-Fc1 locus in modifying the disease course of MS.

Cognitive impairment in MS impacts negatively on many patients at all disease stages and in all subtypes. Full clinical cognitive assessment is expensive, requiring expert staff and special equipment. Test versions and normative data are not available for all languages and cultures. A brief cognitive assessment for MS has been recommended. A validation protocol has been prepared for language groups and validation studies have commenced.

Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the human central nervous system. While the clinical impact of gray matter pathology in MS brains is unknown, 30–40% of MS patients demonstrate memory impairment. The molecular basis of this memory dysfunction has not yet been investigated in MS patients.

Cerebral atrophy is a correlate of clinical progression in multiple sclerosis (MS). Mitochondria are now established to play a part in the pathogenesis of MS. Uniquely, mitochondria harbor their own mitochondrial DNA (mtDNA), essential for maintaining a healthy central nervous system. We explored mitochondrial respiratory chain activity and mtDNA deletions in single neurons from secondary progressive MS (SPMS) cases.

Histone deacetylase 3 (HDAC3) belongs to a family of proteins which plays an important role in protein acetylation, chromatin remodeling and transcription of genes, including those that are involved in cell proliferation and cell death. While increased expression of HDAC3 is seen in neoplastic cells, the role of HDAC3 in T cells and their role in autoimmune disease is not known. MS patients, when compared to controls, show an increased expression of HDAC3 and relative resistance to TSA induced apoptosis in T cells. Increased expression of HDAC3 in PBMC of MS patients may render putative autoreactive lymphocytes resistance to apoptosis and thereby contribute to autoimmunity.

Numerous cytokines are implicated in the immunopathogenesis of multiple sclerosis (MS), but studies are often limited to whole blood (WB) or peripheral blood mononuclear cells (PBMCs), thereby omitting important information about the cellular origin of the cytokines. Knowledge about the relation between blood and cerebrospinal fluid (CSF) cell expression of cytokines and the cellular source of CSF cytokines is even more scarce. In CSF-cell studies, B-cells appear to be enriched in RRMS and associated with expression of pro-inflammatory cytokines; contrarily, monocytes are relatively scarce in CSF from RRMS patients and are associated with IL10 expression. Thus, our findings suggest a pathogenetic role of B-cells and an immunoregulatory role of monocytes in RRMS.

As SHP-1 is deficient in MS leukocytes and SHP-1-regulated proinflammatory genes are correspondingly upregulated, we propose that increased SHP-1 promoter methylation may relate in part to decreased SHP-1 expression and increased leukocyte-mediated inflammation in MS.

The protective haplotype for MS in STAT3 is a risk allele for Crohn disease, implying that STAT3represents a shared risk locus for at least two autoimmune diseases. This study also demonstrates the potential of special isolated populations in search for variants contributing to complex traits.

Cognitive impairment occurs in children and adolescents with multiple sclerosis: results from a United States network.
In the largest sample studied to date, we measured cognitive functioning in children and adolescents with pediatric multiple sclerosis (n = 187) as well as those with clinically isolated syndrome (n = 44). A diagnosis of multiple sclerosis (odds ratio = 3.60, confidence interval = 1.07, 12.36, P = .04) and overall neurologic disability (odds ratio = 1.47, confidence interval = 1.10, 2.10, P = .03) were the only independent predictors of cognitive impairment. Cognitive impairment may occur early in these patients, and prompt recognition is critical for their care.

Progressive degeneration of the retinal nerve fiber layer in patients with multiple sclerosis.
To quantify changes in the retinal nerve fiber layer (RNFL) of patients with multiple sclerosis (MS) over 3 years and to evaluate whether treatment protects against RNFL degeneration. Progressive axonal loss can be detected in the optic nerve fiber layer of MS patients. Analysis of the RNFL by OCT can be useful for evaluating MS progression and efficacy of treatment as a neuroprotective factor against axonal degeneration.

Environmental factors and their regulation of immunity in multiple sclerosis.
Epidemiological and clinical studies have shown that environmental factors such as infections, smoking and vitamin D are associated with the risk of developing multiple sclerosis (MS). Some of these factors also play a role in the MS disease course. We are currently beginning to understand how environmental factors may impact immune function in MS on a cellular and molecular level. Here we review epidemiological, clinical and basic immunological studies on the environmental factors, viral and parasitic infections, smoking, and vitamin D and relate epidemiological findings with their likely pathophysiology in MS.

Gait variability and disability in multiple sclerosis.
Gait variability is clinically relevant in some populations, but there is limited documentation of gait variability in persons with multiple sclerosis (MS). EDSS was positively correlated with step length variability and individuals with MS who used assistive devices to walk had significantly greater step length variability than those who walked independently (p's<.05). EDSS was correlated with step time and length variability even when age was taken into account. Additionally, Fisher's z test of partial correlations revealed that average gait parameters were more closely related to disability status than gait variability in individuals with MS. This suggests that focusing on average gait parameters may be more important than variability in therapeutic interventions in MS.

Genetic and infectious profiles of Japanese multiple sclerosis patients.
Nationwide surveys conducted in Japan over the past thirty years have revealed a four-fold increase in the estimated number of multiple sclerosis (MS) patients, a decrease in the age at onset, and successive increases in patients with conventional MS, which shows an involvement of multiple sites in the central nervous system, including the cerebrum and cerebellum. We aimed to clarify whether genetic and infectious backgrounds correlate to distinct disease phenotypes of MS in Japanese patients. Our study suggests that MS patients harboring DRB1*0405, a genetic risk factor for MS in the Japanese population, have a younger age at onset and a relatively benign disease course, while DRB1*0405-negative MS patients have features similar to Western-type MS in terms of association with Epstein-Barr virus infection and DRB1*1501. The recent increase of MS in young Japanese people may be caused, in part, by an increase in DRB1*0405-positive MS patients.

Benign course of tumour-like multiple sclerosis. Report of five cases and literature review.Multiple sclerosis (MS) with initial neuroradiological features suggestive of brain tumour (tumour-like MS) may represent a challenging diagnosis. Our report of clinical, radiological and pathological features of five tumour-like MS cases confirms that it is mandatory to consider a demyelinating process in the differential diagnosis of tumour-like brain lesions. Many tumour-like MS cases may have a favourable long term prognosis.

A gender-related action of IFNbeta-therapy was found in multiple sclerosis.
Understanding how sexual dimorphism affects the physiological and pathological responses of the immune system is of considerable clinical importance and could lead to new approaches in therapy. Sexual dimorphism has already been noted as an important factor in autoimmune diseases: the aim of this study was to establish whether sexual dimorphism in autoimmune diseases is the result of differing pathways being involved in the regulation of T-helper (Th) cell network homeostasis.
The identification of gender-specific drugs is of considerable importance in translational medicine and will undoubtedly lead to more appropriate therapeutic strategies and more successful treatment.

Suicide risk in multiple sclerosis: a systematic review of current literature.
Studies have shown that suicidal ideation is often revealed among patients suffering from Multiple Sclerosis (MS). Mental health assessment of physically ill patients should form part of routine clinical evaluation, particularly in chronic illness. Clinicians should be aware of the fact that suicidality may occur with higher frequency in MS patients, the available data suggest that the risk of self-harm is higher than expected in MS patients.

OTC Meds May Prevent Marijuana-Induced Memory Problems
"Our results suggest that the unwanted side effects of cannabis could be eliminated or reduced, while retaining its beneficial effects, by administering a COX-2 inhibitor along with THC for the treatment of intractable medical conditions," Dr. Chen summarized.

Increased B cell and cytotoxic NK cell proportions and increased T cell responsiveness in blood of natalizumab-treated multiple sclerosis patients.
Changes in the blood lymphocyte composition probably both mediate and reflect the effects of natalizumab treatment in multiple sclerosis, with implications for treatment benefits and risks.
Our data confirms that natalizumab treatment increases the number of lymphocytes in blood, likely mirroring the expression of VLA-4 being highest on NK and B cells. This finding supports reduction of lymphocyte extravasation as a main mode of action, although the differential effects on subpopulation composition suggests that cell-signalling may also be affected. The systemic increase in T cell responsiveness reflects the increase in numbers, and while augmenting anti-infectious responses systemically, localized responses may become correspondingly decreased.

Analysis of CYP27B1 in multiple sclerosis.
he analysis of genetic variability in CYP27B1 and its effect on risk of multiple sclerosis (MS) has yielded conflicting results. Here we describe a study to genetically characterize CYP27B1 and elucidate its role on MS risk in the Canadian population. Sequencing CYP27B1 failed to identify mutations known to cause loss of enzymatic activity, however genotyping of p.R389H in cases and controls identified the mutation in one multi-incident family (allele frequency=0.03%) in which the p.R389H mutation segregates with disease in five family members diagnosed with MS, thus providing additional support for CYP27B1 p.R389H in the pathogenicity of MS.

Daclizumab, an IL-2 modulating antibody for treatment of multiple sclerosis.
In recently completed randomized trials in RRMS, treatment with daclizumab monotherapy compared with placebo resulted in clinically meaningful and statistically significant reductions in relapses, active lesions on brain MRI and slowing of disability progression. A large Phase III trial in RRMS is ongoing.

Association between multiple sclerosis and epilepsy: large population-based record-linkage studies.Multiple sclerosis (MS) and epilepsy are both fairly common and it follows that they may sometimes occur together in the same people by chance. We sought to determine whether hospitalisation for MS and hospitalisation for epilepsy occur together more often than expected by chance alone. MS and epilepsy occur together more commonly than by chance. One possible explanation is that an MS lesion acts as a focus of an epileptic seizure; but other possibilities are discussed. Clinicians should be aware of the risk of epilepsy in people with MS. The findings may also suggest clues for researchers in developing hypotheses about underlying mechanisms for the two conditions.

Present and future of fMRI in multiple sclerosis.
As shown in brain studies, these investigations have detected increased recruitment in MS patients compared with healthy controls. At present, fMRI is a useful research tool, and reliable analysis and display methods have been developed. Future perspectives include development of fMRI paradigms for patients with MS-related disability and application of this technique in longitudinal studies to define the temporal evolution of functional cortical changes in different MS phenotypes as well as the effects of various therapeutic approaches on central nervous system plasticity.

Decoding multiple sclerosis: an update on genomics and future directions.
Ongoing efforts to fully characterize the repertoire of genes that predispose to MS and modulate its presentation is discussed. Functional characterization of even a moderate genetic effect on MS pathogenesis by a known gene or group of genes can assist in elucidating fundamental mechanisms of disease expression and yield important therapeutic opportunities.

Automated extraction of clinical traits of multiple sclerosis in electronic medical records.
The clinical course of multiple sclerosis (MS) is highly variable, and research data collection is costly and time consuming. We evaluated natural language processing techniques applied to electronic medical records (EMR) to identify MS patients and the key clinical traits of their disease course. This collection of clinical data represents one of the largest databases of detailed, clinical traits available for research on MS. This work demonstrates that detailed clinical information is recorded in the EMR and can be extracted for research purposes with high reliability.

Cortical disease has emerged as a critical aspect of the pathogenesis of multiple sclerosis, being associated with disease progression and cognitive impairment. Most studies of cortical lesions have focused on autopsy findings in patients with long-standing, chronic, progressive multiple sclerosis, and the noninflammatory nature of these lesions has been emphasized. Magnetic resonance imaging studies indicate that cortical damage occurs early in the disease.

Macular oedema typically results from blood–retinal barrier disruption. It has recently been reported that patients with multiple sclerosis treated with FTY-720 (fingolimod) may exhibit macular oedema. Multiple sclerosis is not otherwise thought to be associated with macular oedema except in the context of comorbid clinical uveitis. Despite a lack of myelin, the retina is a site of inflammation and microglial activation in multiple sclerosis and demonstrates significant neuronal and axonal loss.

Many promising MRI approaches for research or clinical management of multiple sclerosis (MS) have recently emerged, or are under development or refinement. Advanced MRI methods need to be assessed to determine whether they allow earlier diagnosis or better identification of phenotypes. Improved post-processing should allow more efficient and complete extraction of information from images.

Magnetic resonance imaging (MRI) of lesions in the brain may be the best current candidate for a surrogate biological marker of clinical outcomes in relapsing remitting multiple sclerosis (MS), based on its role as an objective indicator of disease pathology. No biological surrogate marker has yet been validated for MS clinical outcomes. Confidence intervals for correlations between CELs and MS relapses exclude the possibility that CELs can be a good surrogate for relapses over the time scales we investigated. Further exploration of surrogacy between MRI measures and MS clinical outcomes may require improved datasets, the development of MRI techniques that couple better to clinical disease, and the ability to test a wide range of imaging- and clinically-based hypotheses for surrogacy.

Increasingly, evidence-based health information, in particular evidence from systematic reviews, is being made available to lay audiences, in addition to health professionals. Research efforts have focused on different formats for the lay presentation of health information. However, there is a paucity of data on how patients integrate evidence-based health information with other factors such as their preferences for information and experiences with information-seeking. The aim of this project is to explore how people with multiple sclerosis (MS) integrate health information with their needs, experiences, preferences and values and how these factors can be incorporated into an online resource of evidence-based health information provision for people with MS and their families.

Multiple sclerosis (MS) is an inflammatory neurodegenerative disease of the CNS for which only partially effective therapies exist. Intense research defining the underlying immune pathophysiology is advancing both the understanding of MS as well as revealing potential targets for disease intervention. Mesenchymal stromal cell (MSC) therapy has the potential to modulate aberrant immune responses causing demyelination and axonal injury associated with MS, as well as to repair and restore damaged CNS tissue and cells.

White matter (WM) and grey matter (GM) brain damage in multiple sclerosis (MS) is widespread, but the extent of cerebellar involvement and impact on disability needs to be clarified.These findings indicate reduced fibre coherence in the main cerebellar connections, and link damage in the whole cerebellar WM, and, in particular, in the superior cerebellar peduncle, to motor deficit in PPMS.

Despite significant progress in the development of therapies for relapsing MS, progressive MS remains comparatively disappointing. Our objective, in this paper, is to review the current challenges in developing therapies for progressive MS and identify key priority areas for research. A collaborative was convened by volunteer and staff leaders from several MS societies with the mission to expedite the development of effective disease-modifying and symptom management therapies for progressive forms of multiple sclerosis.

Susac syndrome, a rare but probably underdiagnosed combination of encephalopathy, hearing loss, and visual deficits due to branch retinal artery occlusion of unknown aetiology has to be considered as differential diagnosis in various conditions. Particularly, differentiation from multiple sclerosis is often challenging since both clinical presentation and diagnostic findings may overlap. Optical coherence tomography is a powerful and easy to perform diagnostic tool to analyse the morphological integrity of retinal structures and is increasingly established to depict characteristic patterns of retinal pathology in multiple sclerosis. Against this background we hypothesised that differential patterns of retinal pathology facilitate a reliable differentiation between Susac syndrome and multiple sclerosis.

A Transdermal Myeloid Peptide Patch to Treat MS
Although antigen-specific autoimmunity is thought to play a critical role in the pathogenesis of multiple sclerosis, all currently available therapies reduce global immune function without targeting the specific antigens involved. The goal of this 1-year, double-blind, placebo-controlled cohort study was to examine the efficacy and safety of transdermally applied myelin peptides as antigen-specific therapy in multiple sclerosis.

Sjögren Syndrome: An A-to-Z Update
A steady growth in the number of abstracts and sessions devoted to Sjögren syndrome is apparent over the past decade of ACR meetings. It is encouraging that many pharmaceutical companies are now expressing interest in Sjögren syndrome as a therapeutic target. The dearth of effective therapies for systemic manifestations of Sjögren syndrome contrasts with the large number of therapies for rheumatoid arthritis and studies for psoriatic arthritis. Multiple sclerosis and fibromyalgia have also benefited from recently approved therapies.

Synaptic plasticity in multiple sclerosis and in experimental autoimmune encephalomyelitis.
Approximately half of all patients with multiple sclerosis (MS) experience cognitive dysfunction, including learning and memory impairment. Recent studies suggest that hippocampal pathology is involved, although the mechanisms underlying these deficits remain poorly understood. Evidence obtained from a mouse model of MS, the experimental autoimmune encephalomyelitis (EAE), suggests that in the hippocampus of EAE mice long-term potentiation (LTP) is favoured over long-term depression in response to repetitive synaptic activation, through a mechanism dependent on enhanced IL-1β released from infiltrating lymphocytes or activated microglia.

The risk of Bipolar Disorders in Multiple Sclerosis.
The aim was to determine the risk of Mood Disorders (MD), particularly Bipolar Disorders (BD), in Multiple Sclerosis (MS) using standardized psychiatric diagnostic tools. This study was the first to show an association between BD and MS using standardized diagnostic tools and a case-control design. The results suggest a risk of under-diagnosis of BD (particularly type II) in MS and caution in prescribing ADs to people with depressive episodes in MS without prior excluding BD. The association between auto-immune degenerative diseases (like MS) and BD may be an interesting field for the study of the pathogenic hypothesis.

Long-term effects of dalfampridine in patients with multiple sclerosis.
Dalfampridine is the extended-release formulation of 4-aminopyridine and is approved for the symptomatic treatment of impaired mobility in patients with multiple sclerosis. Our aim was to examine the short- and long-term effects of treatment with dalfampridine on motoric and cognitive assessment parameters of multiple sclerosis (MS) patients over 9-12months. Dalfampridine shows positive short- and long-term effects on motoric and cognitive assessment parameters in an open-label observational study in a cohort of patients with MS.

Oxidative modification of blood serum proteins in multiple sclerosis after interferon or mitoxantrone treatment.
his study was aimed at (i) comparison of the usefulness of serum protein oxidation parameters for assessment of oxidative stress (OS) in multiple sclerosis (MS), and (ii) comparison of OS in MS patients subject to various therapies. Elevated glycophore level was noted in relapsing-remitting (RRMS) patients without treatment and patients treated with interferons β1a and β1b (10.33±3.27, 8.02±2.22 and 8.56±2.45 vs control 5.27±0.73 fluorescence units (FU)/mg protein).

Cross-sectional area variations of internal jugular veins during supine head rotation in multiple sclerosis patients with chronic cerebrospinal venous insufficiency: a prospective diagnostic controlled study with duplex ultrasound investigation.
Normally, chronic cerebrospinal venous insufficiency (CCSVI) has been studied using echo-colour Doppler (ECD). Subjects are examined in the supine and sitting positions, in accordance with a static protocol without rotation of the head. A dynamic approach, to assess venous sizes with different degrees of head rotation, has only been performed to improve jugular venous catheterisation. These echographic studies have suggested that head rotation to the contralateral side increases the cross-sectional area (CSA) of the internal jugular veins (IJVs) in supine subjects. Our goal was to evaluate the behaviour of CSA of the IJVs during supine head rotation in multiple sclerosis (MS) patients with CCSVI, compared to healthy controls (HCs). A dynamic ECD approach allowed us to detect IJVs with a significant increase in their CSAs during head rotation, but only in MS subjects. This feature, most likely the expression of congenital wall miopragia, could be secondary to dysregulation of collagen synthesis, but further histochemical studies will be needed to confirm this hypothesis.

Assessment of upper limb motor function in patients with multiple sclerosis using the Virtual Peg Insertion Test: A pilot study.
Quantifying and tracking upper limb impairment is of key importance to the understanding of disease progress, establishing patient-tailored therapy protocols and for optimal care provision. This paper presents the results of a pilot study on the assessment of upper limb motor function in patients with multiple sclerosis (MS) with the Virtual Peg Insertion Test (VPIT). The test consists in a goal-directed reaching task using a commercial haptic display combined with an instrumented handle and virtual environment, and allows for the extraction of objective kinematic and dynamic parameters.

Novel Immunomodulatory Approaches for the Management of Multiple Sclerosis.
We provide a focused review of novel immunomodulatory approaches for the treatment of multiple sclerosis, the most common acquired inflammatory demyelinating disease of humans. The requirement for such a review was stimulated by the emerging application of novel oral medications and the need for the practicing physician to place these within the treatment paradigm.

A nine-year population-based cohort study on the risk of multiple sclerosis in patients with optic neuritis.
Patients with optic neuritis (ON) are at an increased risk of developing multiple sclerosis (MS), an illness that may result in physical dysfunction and short life expectancy. Information on the conversion rate to MS of patients with ON is essential in determining the impact of ON on the incidence of MS. Previous Taiwanese studies on the risk of MS in patients with ON were all hospital based, thereby limiting the generalizability of the findings.

Mood and coping in clinically isolated syndrome and multiple sclerosis.
Few studies have examined behavioural changes in the early phase of multiple sclerosis (MS). The aim of the study is to investigate mood alterations and to explore coping strategies regarding patients with clinically isolated syndrome (CIS) and relapsing-remitting MS (RRMS). This study highlights transient mood alterations and an improving of adaptive coping over a period of time in patients with CIS and RRMS. Similar emotional reactions and coping in clinical subgroups suggest that these factors are independent from the type of information provided during the communication of the diagnosis.

Improvement of driving skills in persons with Relapsing-Remitting Multiple Sclerosis: a pilot study.
To determine the potential to improve driving-related skills using a simulator-based program in persons with Relapsing Remitting Multiple Sclerosis (RRMS). This pilot study demonstrates the potential of using a simulator to improve driving-related visual, cognitive, and on-road skills in individuals with RRMS, particularly those with EDSS > 3. Future randomized controlled trials with adequate power are needed to expand this field of study.

Risk evaluation and monitoring in multiple sclerosis therapeutics.
Risk for multiple sclerosis (MS) disease-modifying therapies (DMT) must be assessed on an ongoing basis. Early concerns regarding the first-approved DMTs for MS have been mitigated, but recently licensed therapies have been linked to possibly greater risks. It is difficult to produce a general risk-assessment algorithm for all MS therapies. Specific algorithms are required for each DMT in every treated-patient population. New and evolving risks must be evaluated and communicated rapidly to allow patients and physicians to be well informed and able to share treatment decisions.

Five-year results from a phase 2 study of oral fingolimod in relapsing multiple sclerosis.
We present here results at 60 months (M), from the extension component of a phase 2, randomized, placebo-controlled, double-blind, six-month study evaluating oral fingolimod (1.25 mg or 5 mg daily) in relapsing multiple sclerosis. Placebo patients from the core study were re-randomized to fingolimod 1.25 mg or 5 mg in the extension. All patients received 1.25 mg fingolimod after the M24 visit. A total of 140/281 (49.8%) patients completed M60. Fingolimod treatment was associated with a low annualized relapse rate (0.2 relapses/ year), low MRI activity, and a modest rate of disability progression in those treated for five years. No new safety issues were reported.

The reliability and validity study of the Kinesthetic and Visual Imagery Questionnaire in individuals with Multiple Sclerosis.
Motor imagery (MI) has been recently considered as an adjunct to physical rehabilitation in patients with multiple sclerosis (MS). It is necessary to assess MI abilities and benefits in patients with MS by using a reliable tool. The Kinesthetic and Visual Imagery Questionnaire (KVIQ) was recently developed to assess MI ability in patients with stroke and other disabilities. Considering the different underlying pathologies, the present study aimed to examine the validity and reliability of the KVIQ in MS patients. The results of the present study revealed that the KVIQ is a valid and reliable tool for assessing MI in MS patients.

Pregnancy and Fetal Outcomes After Glatiramer Acetate Exposure in Patients With Multiple Sclerosis
Only few studies have assessed safety of in utero exposure to glatiramer acetate (GA). Following a previous study assessing the safety of interferon beta (IFNB) pregnancy exposure in multiple sclerosis (MS), we aimed to assess pregnancy and fetal outcomes after in utero exposure to GA, using the same dataset, with a specific focus on the risk of spontaneous abortion. Data in our cohort show that mother's GA exposure is not associated with a higher frequency of spontaneous abortion, neither other negative pregnancy and fetal outcomes. Our findings point to the safety of in utero GA exposure and can support neurologists in the therapeutic counselling of MS women planning a pregnancy.

Smoking and Two Human Leukocyte Antigen Genes Interact to Increase the Risk for Multiple Sclerosis
Both genetic and environmental factors display low or modest associations with multiple sclerosis. Hypothetically, gene–environment interactions may exert much stronger effects. In this study, we investigated potential interactions between genetic risk factors and smoking in relation to risk of developing multiple sclerosis. A population-based case–control study involving incident cases of multiple sclerosis (843 cases, 1209 controls) was performed in Sweden. Cases and controls were classified according to their smoking status and human leukocyte antigen DRB1 as well as human leukocyte antigen A genotypes.

The month of birth effect in multiple sclerosis: systematic review, meta-analysis and effect of latitude.Month of birth has previously been described as a risk factor for multiple sclerosis (MS). This has been hypothesised to be related to maternal vitamin D levels during pregnancy, although conclusive evidence to support this is lacking. To date, no large studies of latitudinal variation in the month of birth effect have been performed to advance this hypothesis. Month of birth has a significant effect on subsequent MS risk. This is likely to be due to ultraviolet light exposure and maternal vitamin D levels, as demonstrated by the relationship between risk and latitude.

Carnitine for fatigue in multiple sclerosis.
Fatigue is reported to occur in up to 92% of patients with multiple sclerosis (MS) and has been described as the most debilitating of all MS symptoms by 28% to 40% of MS patients. There is insufficient evidence that carnitine for the treatment of MS-related fatigue offers a therapeutic advantage over placebo or active comparators. Results of the ongoing trial are eagerly anticipated in order to provide clarity.

Objectively quantified physical activity in persons with multiple sclerosis.
To investigate levels of moderate-to-vigorous physical activity (MVPA) in a large sample of persons with multiple sclerosis (MS) and controls using accelerometry as a measure of physical activity, and to compare the rates of meeting public health guidelines for MVPA (ie, 30min/d) between persons with MS and controls. We provide data using an objective physical activity measure and a large sample to indicate that only a small proportion of persons with MS are achieving adequate amounts of daily MVPA.

To review patients with tumefactive MS and compare them with those in other studies investigating tumefactive demyelinating lesions and our Taiwanese typical MS patients. Tumefactive MS is not common in Taiwan. Although the tumefactive demyelinating lesions seem to be terrible initially, their prognosis is relatively more favorable than expected.

Prevalence and incidence of Multiple Sclerosis in Campobasso (Molise region chieftown, southern Italy).
Multiple Sclerosis in southern Italy was not epidemiologically studied until 2006 in Salerno (Campania region), with data based on the registry of district MS centers established since 1996 by Italian Ministry of Health. This paper reports data about Molise region by the same metodology as Campanian study. Prevalence is coherent with previous Campanian data, and with last epidemiologic papers on middle Italy, confirming also the validity of MS district centers registries. A possible underestimation of data, for some patients could still migrate to northern centers, could contribute to the differences in incidence. Nevertheless, prevalence data confirm southern Italy as high risk area for MS, and stands against a latitude gradient in this country.

First-line disease-modifying drugs for the treatment of multiple sclerosis (MS) are mostly administered by injection. Although these treatments can control the symptoms and progression of the disease to some extent, patients often fail to adhere to their therapy in the long term, so may not obtain the maximum clinical benefits. As injection-related problems are common barriers to adherence, autoinjectors have been developed to improve the ease and convenience of self-injection.
The device is the first electronic autoinjector for use in MS and offers several innovative features, including adjustable injection settings and an electronic dosing log, which may improve adherence. The dosing log can be reviewed with the patient, allowing the physician to open a dialogue to discuss possible issues with treatment adherence. The use of multidose cartridges also provides a softer impact on the environment and easier disposal. The hidden needle helps avoid needle phobia and reduces the risk of needle stick injury.

Drug Class Review: Disease-modifying Drugs for Multiple Sclerosis: Final Update 1 Report [Internet].
We compared the effectiveness and safety of disease-modifying drugs for the treatment of multiple sclerosis: Glatiramer acetate (Copaxone®), interferon beta-1a (Avonex®, Rebif®), interferon beta-1b (Betaseron®, Extavia®), mitoxantrone (Novantrone®), and natalizumab (Tysabri®). There was fair evidence that interferon beta-1a IM (Avonex®) is less effective than interferon beta-1a SC (Rebif®) and interferon beta-1b (Betaseron®) for preventing relapse in patients with relapsing remitting multiple sclerosis. On other outcomes and in other populations, direct evidence is either lacking or shows few differences in effectiveness or safety among the disease-modifying drugs used to treat multiple sclerosis.

Association of UV radiation with multiple sclerosis prevalence and sex ratio in France.
French farmers and their families constitute an informative population to study multiple sclerosis (MS) prevalence and related epidemiology. We carried out an ecological study to evaluate the association of MS prevalence and ultraviolet (UV) radiation, a candidate climatologic risk factor.
The findings suggest that regional UVB radiation is predictive of corresponding MS prevalence rates and supports the hypothesis that sunlight exposure influences MS risk. The evidence also supports a potential role for gender-specific effects of UVB exposure.

The polymorphisms of the TNF-α gene in multiple sclerosis?--a meta-analysis.
The association between multiple sclerosis (MS) and tumor necrosis factor-alpha gene (TNF-α) polymorphisms has been analyzed in several studies, but conflicting results have been reported. The main purpose of this study was to integrate previous findings and explore whether the three single nucleotide polymorphisms (SNPs; -238G/A, -308G/A, and -376G/A) of TNF-α are associated with susceptibility to MS. A total of 2,639 patients and 3,303 controls from 21 studies, which were identified by searching the ISI Web of Knowledge database and the PubMed database up to December 2009, were collected for this meta-analysis.

Treatment of Multiple Sclerosis With Chinese Scalp Acupuncture.
Chinese scalp acupuncture is a contemporary acupuncture technique with just 40 years of history. It integrates traditional Chinese needling methods with Western medical knowledge of the cerebral cortex and has been proven to be a very effective technique for treating multiple sclerosis (MS) and other central nervous system disorders. A 65-year-old male patient who had had MS for 20 years was treated with Chinese scalp acupuncture. The motor area, sensory area, foot motor and sensory area, balance area, hearing and dizziness area, and tremor area were stimulated once a week for 10 weeks, then once a month for six sessions. After the 16 treatments, the patient showed remarkable improvements. He was able to stand and walk without any problems. The numbness and tingling in his limbs did not bother him anymore. He had more energy and had not experienced incontinence of urine or dizziness after the first treatment. He was able to return to work full time. At this writing, the patient has been in remission for 26 months. This case demonstrates that Chinese scalp acupuncture can be a very effective treatment for patients with MS. Chinese scalp acupuncture holds the potential to expand treatment options for MS in both conventional and complementary or integrative therapies. It can not only relieve symptoms, increase the patient's quality of life, and slow and reverse the progression of physical disability but also reduce the number of relapses and help patients with multiple sclerosis to remain in remission.

Genetic burden of common variants in progressive and bout-onset multiple sclerosis.
The contribution of genetic variants underlying the susceptibility to different clinical courses of multiple sclerosis (MS) is still unclear. Our results suggest that the liability of disease is better captured by common genetic variants in BOMS than PrMS cases. The absence of inflammatory activity and male gender further raise the difference between clinical courses.

Combination of robot-assisted and conventional body-weight-supported treadmill training improves gait in persons with multiple sclerosis: a pilot study.
The majority of persons with multiple sclerosis (MS) experience problems with gait, which they characterize as highly disabling impairments that adversely impact their quality of life. Thus, it is crucial to develop effective therapies to improve mobility for these individuals. The purpose of this study was to determine whether combination gait training, using robot-assisted treadmill training followed by conventional body-weight-supported treadmill training within the same session, improved gait and balance in individuals with MS. Combination of robot with body-weight-supported treadmill training gait training is feasible and improved 6MWT and FRT distances in persons with MS.Video Abstract available (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A62) for more insights from the authors.

Multiple sclerosis (MS) is a chronic autoimmune disease that targets myelinated axons in the central nervous system. Headache has been reported as a subtle symptom of the onset of MS, with a variable frequency of 1.6–28.5%; however, it remains unclear whether headache is a true symptom of MS onset. Here, we report the case of a female patient who had a history of migraine without aura and experienced worsening of migraine-headache symptoms as the initial manifestation of MS. Three similar cases were reported previously; however, unlike this case, those cases had no history of migraine without aura.

To investigate the presence and the nature of cognitive impairment in a large sample of patients with Multiple Sclerosis (MS), and to identify clinical and demographic determinants of cognitive impairment in MS. Our results corroborate the evidence about the presence and the nature of cognitive impairment in a large sample of patients with MS. Furthermore, our findings identify significant clinical and demographic determinants of cognitive impairment in a large sample of MS patients for the first time. Implications for further research and clinical practice were discussed.

Multiple sclerosis (MS) is universally found to be more prevalent in women than men. This has led to extensive studies of differences in the immune system or nervous system between women and men, which might be caused by the effects of gonadal hormones, genetic differences, and different environmental exposures and modern lifestyle in men and women. We review the effects of sex and gender from a genetic, immunological and clinical point of view. We discuss the effects of sex on the clinical expression of MS and responses to therapy, as well as issues concerning pregnancy.

The study of muscle metabolism by near-infrared spectroscopy (NIRS) has been poorly implemented in multiple sclerosis (MS). Aims of the study were to compare resting muscle oxygen consumption (rmVO2) at gastrocnemius in MS patients and in age-matched healthy controls (HC) measured using NIRS, and to evaluate its possible relationship with patients’ mobility.

Background. Many people with MS fall, but the best method for identifying those at increased fall risk is not known. Objective. To compare how accurately fall history, questionnaires, and physical tests predict future falls and injurious falls in people with MS. Methods. 52 people with MS were asked if they had fallen in the past 2 months and the past year. Subjects were also assessed with the Activities-specific Balance Confidence, Falls Efficacy Scale-International, and Multiple Sclerosis Walking Scale-12 questionnaires, the Expanded Disability Status Scale, Timed 25-Foot Walk, and computerized dynamic posturography and recorded their falls daily for the following 6 months with calendars. The ability of baseline assessments to predict future falls was compared using receiver operator curves and logistic regression. Results. All tests individually provided similar fall prediction (area under the curve (AUC) 0.60–0.75). A fall in the past year was the best predictor of falls (AUC 0.75, sensitivity 0.89, specificity 0.56) or injurious falls (AUC 0.69, sensitivity 0.96, specificity 0.41) in the following 6 months. Conclusion. Simply asking people with MS if they have fallen in the past year predicts future falls and injurious falls as well as more complex, expensive, or time-consuming approaches.

Several studies have demonstrated benefits of rehabilitation in multiple sclerosis (MS). However, the neuroscientific foundations for rehabilitation in MS are poorly established. Mechanisms for short- and long-term plasticity may compensate for impaired functional connectivity in MS to mediate behavioural improvements. Future studies are needed to define the neurobiological substrates of this plasticity and the extent to which mechanisms of plasticity in patients may be distinct from those used for motor learning in controls.

Sexual Dysfunction in Male Patients with Multiple Sclerosis: A Need for Counseling!
Sexuality and sexual health are significant factors in determining the quality of life (QoL). Multiple sclerosis (MS) is one of the most serious causes of neurological disability in young adults, therefore it can considerably reduce sexuality. Physical and cognitive symptoms of MS as well as mental and psycho-social issues can directly affect sexual life and body representation, causing reduced libido and self-esteem. Male patients with MS frequently develop sexual dysfunction (SD) as a result of their neurological impairment: in fact physical, psychological and neuropsychological changes indirectly interfere in the sexual response. Thus, MS physicians' greater concern on SD has led to the enhancement of diagnostic and therapeutic diagnoses on neurogenic SD. Given the increasing number of people coping with MS, a more effective focus on MS-related problems, including SD, is absolutely essential to provide the patients and their partner with the necessary information to achieve a better sexual health and consequently improve their QoL. This review aims to investigate the epidemiology and pathophysiology of SD in male patients, provide an insight into multidisciplinary diagnostic and therapeutic approaches, and focus on the need of proper counseling.

[Paroxysmal dystonia and multiple sclerosis.]
Movement disorders are uncommon in multiple sclerosis, except for tremor. Patients rarely have paroxysmal dystonia (or tonic spasm), which can be the presenting manifestation of the disease.
Dystonia is an under-recognized aspect of paroxysmal events during multiple sclerosis. It might involve ephaptic transmission among abnormal demyelinated neurons; this ectopic excitation can arise at variable levels of the corticospinal tract, but the analysis of reported cases and those described in this study shows that impairment of the posterior limb of the internal capsule seems to be a prevalent topography. Inflammation is likely to play a role because steroids often improve these phenomena. In this article, we review the clinical aspects, pathophysiology and outcome of paroxysmal dystonia in multiple sclerosis.

Frequency analysis approach to study balance control in individuals with multiple sclerosis.
The ability to control balance is often compromised in people with multiple sclerosis (MS) and is considered to be a strong contributing factor toward their increased risk of falls. The observed redistribution of the COP power spectrum when vision is absent indicates that people with MS rely more on the vestibular/somatosensory and proprioceptive systems. The outcome of the study suggests that the COP frequency analysis could be used in identifying the possible sources of balance impairment in people with MS.

Multiple sclerosis is an inflammatory, autoimmune, disease of the white mass of the brain, which sometimes may involve the gray matter (subcortical and ones in the anterior horns of the spinal cord) with the chronic nature and generally with progressive course. As a possible cause of this disease state are listed genetic predisposition, early viral infections and environmental factors, with special effects of stress as a provoking factor in first episode of the disease and relapses because stress leads to modulation of the immune system and immune response to various causes. An intensive stressor is certainly one of the triggers for the development of Multiple Sclerosis, as the first episode and worsening of previously established disease.

New understanding, warning signs, and potential treatments for multiple sclerosis
Scientists are gaining a new level of understanding of multiple sclerosis (MS) that may lead to new treatments and approaches to controlling the chronic disease, according to new research released at Neuroscience 2013, the annual meeting of the Society for Neuroscience and the world's largest source of emerging news about brain science and health.

Neuroimaging study sheds light on mechanisms of cognitive fatigue in multiple sclerosis
A new study by Kessler Foundation scientists sheds light on the mechanisms underlying cognitive fatigue in individuals with multiple sclerosis. Cognitive fatigue is fatigue resulting from mental work rather than from physical labor. Genova H et al: Examination of cognitive fatigue in multiple sclerosis using functional magnetic resonance imaging and diffusion tensor imaging" was published in PlosOne. This is the first study to use neuroimaging to investigate aspects of cognitive fatigue. The study was funded by grants from the National MS Society and Kessler Foundation.

A research study headed by Victoria Leavitt, Ph.D. and James Sumowski, Ph.D., of Kessler Foundation, provides the first evidence for beneficial effects of aerobic exercise on brain and memory in individuals with multiple sclerosis (MS). The article, "Aerobic exercise increases hippocampal volume and improves memory in multiple sclerosis: Preliminary findings," was released as an epub ahead of print on October 4 by Neurocase: The Neural Basis of Cognition.

Multiple sclerosis (MS) is a complex autoimmune disease of the central nervous system with a prominent genetic component. The primary genetic risk factor is the human leukocyte antigen (HLA)-DRB1*1501 allele; however, much of the remaining genetic contribution to MS has not been elucidated. The authors investigated the relation between variation in DNA repair pathway genes and risk of MS. Single-locus association testing, epistatic tests of interactions, logistic regression modeling, and nonparametric Random Forests analyses were performed by using genotypes from 1,343 MS cases and 1,379 healthy controls of European ancestry. A total of 485 single nucleotide polymorphisms within 72 genes related to DNA repair pathways were investigated, including base excision repair, nucleotide excision repair, and double-strand breaks repair.

As brain tumours and their treatment may theoretically have a poorer prognosis in inflammatory central nervous system diseases such as multiple sclerosis (MS), all-cause mortality following a brain tumour diagnosis was compared between patients with and without MS. The potential role of age at tumour diagnosis was also examined. Younger age at tumour diagnosis may contribute to mortality reduction in those with high-grade and uncertain-grade brain tumours. Survival following a brain tumour is not worse in patients with MS; even after age at brain tumour diagnosis and grade of malignancy are taken into account.

Fatigue and sleep problems are very commonly observed in patients with multiple sclerosis (MS). The Progressive Muscle Relaxation Technique (PMRT), used as one of the alternative methods in recent years, is reported to have benefits such as facilitating sleep and reducing sensitivity against fatigue. This research was conducted to investigate the effect of PMRT on fatigue and sleep quality in patients with MS. This study supports the effect of PMRT on fatigue and sleep quality in patients with MS, and it is recommended that further studies be conducted on this subject in the future.

The aim of this study was to examine the impact of intravenous methylprednisolone therapy (IVMP) on the recovery of walking ability in patients experiencing multiple sclerosis (MS) relapses, to compare the responsiveness of walking-based measures, and to estimate the impact of different walking-based measures responsiveness on clinical trials. All applied walking-based measures showed significant improvement of walking ability 1 month after the IVMP. Responsiveness of various walking-based measures notably differ, thus affecting sample size calculations.

We investigated the association between chronic cerebrospinal venous insufficiency (CCSVI) and cognitive impairment (CI) in multiple sclerosis (MS). Moreover, we evaluated the association between CCSVI and other frequent self-reported MS symptoms. Our findings suggest a lack of association between CCSVI and CI in MS patients. Fatigue, depressive, bladder/sexual symptoms and self-reported quality of life are not associated with CCSVI.

The efficacy of mitoxantrone induction therapy in rapidly worsening multiple sclerosis (MS) is well established. Plasma exchange is also applied as an adjuvant in exacerbations of relapsing MS. The aim of this study was to compare the efficacy of combination therapy with mitoxantrone and plasma exchange versus mitoxantrone alone in patients with aggressive MS. Administration of mitoxantrone as an induction therapy in patients of aggressive relapsing remitting MS results in significant improvement of their clinical state and MRI activity. However, combination of plasma exchange with mitoxantrone gives no more benefits than mitoxantrone alone and sometimes worsens the situation possibly by reduction of mitoxantrone efficacy as a result of plasma exchange.

Body Mass Index in Multiple Sclerosis: Associations with CSF Neurotransmitter Metabolite Levels.
Body weight and height of patients with relapsing-remitting multiple sclerosis (RRMS) or clinically isolated syndrome suggesting MS (CIS) in the age range 18 to 60 years (154 males and 315 females) were compared with those of subjects (146 males and 212 females) free of any major neurological disease. In drug-free patients, CSF levels of the metabolites of noradrenaline (MHPG), serotonin (5-HIAA), and dopamine (HVA), neurotransmitters involved in eating behavior, were estimated in searching for associations with body mass index (BMI).

Treatment of pediatric multiple sclerosis.
Multiple sclerosis (MS) in children and adolescents has received increased attention during the past decade. Although not tested in randomized placebo-controlled trials, first-line disease-modifying therapies are widely used in patients with MS who are younger than 18 years.

Sodium May Make MS Worse
OPENHAGEN, Denmark — A study for the first time links higher sodium intake with increased clinical and radiologic disease activity in people with multiple sclerosis (MS).
A high-sodium diet has recently been shown to worsen disease in the animal model of MS, experimental autoimmune encephalomyelitis. "Our study adds some evidence that this effect might be also present in humans as individuals that consume high amounts of sodium have a higher number of lesions on MRI and also more clinical bouts," Mauricio Farez, MD, from the Institute for Neurological Research, Buenos Aires, Argentina, told Medscape Medical News.

Omega-3 Fatty Acids of No Benefit in Multiple Sclerosis
The finding, from the 4-year Omega-3 Fatty Acid Treatment in Multiple Sclerosis (OFAMS) trial, goes against those of preliminary studies that suggested omega-3 supplementation would have a protective effect in MS, lead author Øivind Torkildsen, MD, PhD, from Haukeland University Hospital, Bergen, Norway, told Medscape Medical News.

Exercise and Disease Progression in Multiple Sclerosis
It has been suggested that exercise (or physical activity) might have the potential to have an impact on multiple sclerosis (MS) pathology and thereby slow down the disease process in MS patients. The objective of this literature review was to identify the literature linking physical exercise (or activity) and MS disease progression.

Possible Immune Target Identified in Multiple Sclerosis
t is assumed that in MS, the immune system recognizes proteins of the myelin sheath as antigenic, setting in motion an inflammatory reaction resulting in demyelination of the axons, breakdown of the blood-brain barrier, and the formation of lesions. However, the exact target of the immune response involved in MS has continually eluded researchers.

Smoking: Effects on Multiple Sclerosis Susceptibility and Disease Progression
Multiple sclerosis (MS) is associated with both genetic and environmental factors that influence disease susceptibility. Exposure to cigarette smoke is emerging as a viable environmental risk factor for MS that contributes to both increased disease susceptibility and more rapid disease advancement. The relative risk for MS development is approximately 1.5 for smokers compared with nonsmokers. Furthermore, there may be important interactions between smoking, an individual's genetic background, and other environmental risk exposures. This review summarizes the current evidence supporting the association of smoking with MS risk and disease course, with additional comments on causation.

Behavioral Interventions in Multiple Sclerosis
Managing uncertainty is a major challenge associated with the diagnosis of multiple sclerosis (MS). In addition to physical symptoms, neuropsychiatric symptoms are highly prevalent in this disease. Depression in particular is more common in MS than in other chronic diseases. While substantial achievements have been made in the therapy of MS and an increasing number of immunomodulatory treatments are now available, the long-term benefits of these are still a matter of debate. Importantly, while the approved therapies show good efficacy on inflammatory lesions and relapse rate, and may slow certain aspects of disease progression, improvements in function have rarely been reported.

Neurogenesis In The Chronic Lesions Of Multiple Sclerosis
Subcortical white matter in the adult human brain contains a population of interneurons that helps regulate cerebral blood flow. We investigated the fate of these neurons following subcortical white matter demyelination. Immunohistochemistry was used to examine neurons in normal-appearing subcortical white matter and seven acute and 59 chronic demyelinated lesions in brains from nine patients with multiple sclerosis and four controls.

Exercise therapy and multiple sclerosis: a systematic review.
Multiple sclerosis (MS) is an incurable disease, and despite current pharmacologic treatment being effective in reducing relapse rates and lesion burden, there is little evidence that these treatments work as effectively in preventing disability progression. In such cases, non-pharmacologic techniques such as exercise therapy with rehabilitation purposes may play an important role.

Cortical plasticity predicts recovery from relapse in multiple sclerosis.
Relapsing-remitting multiple sclerosis (RRMS) is characterized by the occurrence of clinical relapses, followed by remitting phases of a neurological deficit. Clinical remission after a relapse can be complete, with a return to baseline function that was present before, but is sometimes only partial or absent. Remyelination and repair of the neuronal damage do contribute to recovery, but they are usually incomplete. Synaptic plasticity may contribute to symptom recovery after a relapse in MS; and PAS, measured during a relapse, may be used as a predictor of recovery.

Disclosure of diagnosis of multiple sclerosis in the workplace positively affects employment status and job tenure.
For many employees with multiple sclerosis (MS), disclosure of their diagnosis at work is seen as a high-risk strategy that might lead to diminished perceptions of their capabilities by supervisors and colleagues, if not outright discrimination. The consequence of this mistrust surrounding the disclosure process is that employees with MS may leave it until too late to effectively manage symptoms at work. This study provides the first empirical support for the positive role of disclosure in maintaining employment status, measured both as job retention and tenure in current employment.

Clinical and demographic factors affecting disease severity in patients with multiple sclerosis.
The clinical course of multiple sclerosis (MS) evolves over many years. Its prognosis is highly variable among affected individuals, i.e. while some suffer from early severe disabilities, others remain ambulatory and functional for many years. We used Multiple Sclerosis Severity Score (MSSS) and the new classification for MS severity Herbert et al. introduced in 2006 according to MSSS, to investigate some clinical and demographic factors as potential indicators of disease severity in in MS. Early prediction of disease severity by demographic and clinical features is currently impossible. We need to determine stronger predictors, possibly a combination of demographic, clinical, biomarkers, and imaging findings.

Magnetic Resonance Monitoring of Lesion Evolution in Multiple Sclerosis
Disease activity in multiple sclerosis (MS) is strongly linked to the formation of new lesions, which involves a complex sequence of inflammatory, degenerative, and reparative processes. Conventional magnetic resonance imaging (MRI) techniques, such as T2-weighted and gadolinium-enhanced T1-weighted sequences, are highly sensitive in demonstrating the spatial and temporal dissemination of demyelinating plaques in the brain and spinal cord. Hence, these techniques can provide quantitative assessment of disease activity in patients with MS, and they are commonly used in monitoring treatment efficacy in clinical trials and in individual cases. However, the correlation between conventional MRI measures of disease activity and the clinical manifestations of the disease, particularly irreversible disability, is weak.

The Fluctuating Natural Course of CCSVI in MS Patients and Controls, a Prospective Follow-Up.
OBJECTIVES: A new treatable venous disorder, chronic cerebrospinal venous insufficiency (CCSVI), has been proposed in patients with multiple sclerosis. The natural course of CCSVI has not been examined yet. This is crucial given the fact that surgical procedures are increasingly offered to MS patients to treat venous stenosis.
CONCLUSIONS: ECD examination shows a fluctuating natural course of the extracranial venous haemodynamics, which makes determination of CCSVI by ECD examination unreliable.

Spasticity in patients with multiple sclerosis - clinical characteristics, treatment and quality of life.
Aims: To gain real-life data on demographic and clinical characteristics, treatment patterns, treatment satisfaction and quality-of-life of multiple sclerosis-related spasticity (MSS) in Germany.
Conclusions: Spasticity and its symptoms impair personal well-being and quality-of-life. Treatment of spasticity with drugs and physiotherapy is common, but satisfaction with the currently available anti-spastic pharmacotherapy is low.

The molecular study of IFNβ pleiotropic roles in MS treatment.
MS) is one of the most important autoimmune diseases recognized by demyelination and axonal lesion. It is the most common cause of disability in the young population. Various immunomodulatory and immunosuppressive therapies, including different formulations of interferon beta (IFNβ), glatiramer acetate (GA), mitoxantrone, and natalizumab are available for this disease. However, interferon has been the best prescribed.

Dietary pattern and risk of multiple sclerosis.
It has been suggested that nutrition might play a role in the etiology of multiple sclerosis (MS). However, dietary patterns associated with MS risk are unknown. This study was conducted to compare the dietary patterns of patients with MS and healthy controls to find the relationship between dietary patterns and MS. Our findings showed that the risk of RRMS can be affected by major dietary patterns.

Optical coherence tomography versus visual evoked potential in multiple sclerosispatients.
Optical coherence tomography (OCT) is a non-invasive instrument, which can be used to estimate the thickness of the retinal nerve fibre layer (RNFL) and provides an indirect measurement of axonal destruction in multiple sclerosis (MS). The main aim of this study was to find out any correlations between P100 latency in visual evoked potential (VEP) and RNFL thickness.
OCT does have good correlations with P100 latency, indicating retinal non-myelinated axonal involvement in early stages in addition to the myelinated axonal involvement. However, it cannot be used as the sole test in evaluating visual pathway in optic neuritis and complementary tests as VEPs are recommended.

Reversible therapy-related dysplastic hematopoiesis following Beta Interferon Therapy in Multiple Sclerosis Patients: Report of 2 Cases.
Interferon beta-la and -1b have been increasingly used for the treatment of multiple sclerosis (MS). The most frequent systemic adverse effects are flu-like symptoms. Laboratory abnormalities include asymptomatic leukopenia and elevated hepatic transaminases. Myelodysplastic Syndrome (MDS) refers to a spectrum of hematological disorders which can occur in different situations. Several hematological abnormalities have been reported following interferon therapy. Both of our cases were reversible; although treatment with IFNβ-1a and-1b is safe and well tolerated in the majority of population, we should be careful about this premalignant hematological disorder.

Effect of honey bee venom on lewis rats with experimental allergic encephalomyelitis, a model for multiple sclerosis.
(MS) is a progressive and autoimmune neurodegenerative disease of the central nervous system (CNS). This disease is recognized through symptoms like inflammation, demyelination and the destruction of neurological actions. Experimental allergic encephalomyelitis (EAE) is a widely accepted animal model for MS. EAE is created in animals by injecting the tissue of myelin basic protein (MBP), CNS, or myelin oligodendrocyte glycoprotein (MOG) along with the adjuvant. EAE and MS are similar diseases. Honey Bee venom (Apis mellifera) contains a variety of low and high molecular weight peptides and proteins, including melittin, apamin, adolapin, mast cell degranulating peptide and phospholipase A2.

Mortality following a brain tumour diagnosis in patients with multiple sclerosis.
As brain tumours and their treatment may theoretically have a poorer prognosis in inflammatory central nervous system diseases such as multiple sclerosis (MS), all-cause mortality following a brain tumour diagnosis was compared between patients with and without MS. The potential role of age at tumour diagnosis was also examined. Younger age at tumour diagnosis may contribute to mortality reduction in those with high-grade and uncertain-grade brain tumours. Survival following a brain tumour is not worse in patients with MS; even after age at brain tumour diagnosis and grade of malignancy are taken into account.

Let's rehabilitate cognitive rehabilitation in multiple sclerosis.
Up to 60% of patients with multiple sclerosis (MS) experience cognitive dysfunction, with prominent involvement of complex attention, information processing speed, executive functions, episodic memory, and visuospatial abilities. Since MS-related cognitive deficits can substantially affect a wide range of daily life activities (e.g., work, driving, social integration, and adherence to medication regimens), it is imperative that we identify and develop strategies to alleviate them.

Prevalence of joint contractures and muscle weakness in people with multiple sclerosis.
Abstract Objectives: To investigate the prevalence of joint contracture (limited passive range of joint motion) and muscle weakness in a population with multiple sclerosis (MS). A secondary aim was to establish normative data of functional tests of mobility and balance of people with MS who are still ambulant. These data show that in addition to muscle weakness joint contractures are highly prevalent among people with MS, especially in the ankle joint. This implicates that prevention of contracture is crucial in providing rehabilitation to people with MS. Implications for Rehabilitation Joint contractures are highly prevalent of people with MS, especially in the lower limb, even at an early stage. While many interventions such as stretching and serial casting have been implemented to reduce contractures, there is not yet strong evidence for their effectiveness. Further research is required.

Relating relapse and T2 lesion changes to disability progression in multiple sclerosis: a systematic literature review and regression analysis.
In the treatment of multiple sclerosis (MS), the most important therapeutic aim of disease-modifying treatments (DMTs) is to prevent or postpone long-term disability. Given the typically slow progression observed in the majority of relapsing-remitting MS (RRMS) patients, the primary endpoint for most randomized clinical trials (RCTs) is a reduction in relapse rate. It is widely assumed that reducing relapse rate will slow disability progression. Similarly, MRI studies suggest that reducing T2 lesions will be associated with slowing long-term disability in MS. The objective of this study was to evaluate the relationship between treatment effects on relapse rates and active T2 lesions to differences in disease progression (as measured by the Expanded Disability Status Scale [EDSS]) in trials evaluating patients with clinically isolated syndrome (CIS), RRMS, and secondary progressive MS (SPMS). Treatment differences in relapse reduction and T2 lesions are positively related to differences in disease progression over the first two years of treatment.

Treatment options for patients with multiple sclerosis who have a suboptimal response to interferon-β therapy.
Although the first-line disease-modifying therapies (DMTs) interferon beta and glatiramer acetate have a favourable benefit-to-risk profile, they are only partially effective for treating relapsing-remitting multiple sclerosis (RRMS). The optimization of treatment in patients who do not show a maximum response to first-line therapy is critical for achieving the best long-term outcomes. Treatment strategies for patients with a suboptimal response include switching to another first-line DMT or a second-line DMT. Natalizumab and fingolimod are approved for RRMS with high disease activity in the European Union and Canada. A descriptive comparison of fingolimod and natalizumab is provided in the context of the decision-making process of how and when to switch patients who have a suboptimal response to first-line therapy.

Effect of treadmill training on fatigue in multiple sclerosis: a pilot study.
People with multiple sclerosis (PwMS) tend to be less physically active than the general population. Limited physical activity increases fatigue, possibly affecting other functions such as balance. Treadmill training is a promising method to ameliorate these symptoms. The aim of this study was to assess the effect of treadmill training on fatigue and balance.

Factors affecting bone mineral density in multiple sclerosis patients. BACKGROUND: Multiple sclerosis (MS) is a demyelinating disease which can cause many disabilities for the patient. Recent data suggests that MS patients have higher risk for osteoporosis. This study was performed to investigate if the osteoporosis prevalence is higher in MS patients and to determine the possible factors affecting bone mineral density (BMD).CONCLUSION: As a result of this study, bone loss inevitably occurs in MS patients. The major factor of BMD loss is immobility. Osteoporosis should be managed as part of MS patients' treatment protocols.

Can multiple sclerosis as a cognitive disorder influence patients' dreams?
Dream should be considered as a kind of cognitive ability that is formed parallel to other cognitive capabilities like language. On the other hand, multiple sclerosis (MS) is a complex disease that can involve different aspects of our cognition. Therefore, MS may influence patients' dreams. In fact, we do not know what the importance of dream is in MS, but further studies may introduce dream and dreaming as a sign of improvement or progression in MS disease.The relation between peptide hormones and sex hormone in patients with multiple sclerosis.BACKGROUND: Hormones can play a significant role in the pathogenesis of multiple sclerosis (MS). The aim of this study was to compare levels of ghrelin, leptin, and testosterone hormones of MS patients with healthy subjects, and assess the relationship between levels of peptide hormone and sex hormones in MS patients.CONCLUSION: According to the results, there was no significant difference between peptide and sex hormones of MS patients and healthy persons. Furthermore, there was no significant relationship between peptide and sex hormones of MS patients and healthy persons.

Is serum vitamin D levels associated with disability in patients with newly diagnosed multiple sclerosis?BACKGROUND: Although the precise etiology of multiple sclerosis (MS) is unknown, it seems that both genetic and environmental factors are important. Recent studies suggest that low serum vitamin D levels are important environmental factor in MS. The aim of this study was to compare the serum levels of vitamin D between MS patients and healthy subjects, and to determine its association with disability in MS patients.CONCLUSION: Our findings did not suggest a protective association for serum vitamin D levels against disability in MS patients.

A descriptive comparison of fingolimod and natalizumab is provided in the context of the decision-making process of how and when to switch patients who have a suboptimal response to first-line therapy.

It is well documented that disability accumulation in multiple sclerosis is correlated with axonal injury and that the extent of axonal injury is correlated with the degree of inflammation. However, the interdependence between focal inflammation, diffuse inflammation and neurodegeneration, and their relative contribution to clinical deficits, remains ambiguous.

PRO measures were improved with natalizumab in a real-world setting. The improvements were observed as early as after 3 months and sustained over a 12-month period. The improvements in PROs show that, in clinical practice, the clinical benefits of natalizumab are translated into patient-reported benefits.

Differential diagnosis leading to MS or alternatives is complex and a strong evidence base is lacking. Consensus-determined guidelines provide a practical path for diagnosis and will be useful for the non-MS specialist neurologist. Recommendations are made for future research to validate and support these guidelines. Guidance on the differential diagnosis process when MS is under consideration will enhance diagnostic accuracy and precision.

We demonstrated for the first time, albeit only with preliminary data, the aprioristic possibility of distinguishing naive and IFN-treated MS groups from controls, and naive from IFN-treated MS patients using a blood sample-based methodology (i.e. proteomics) alone. The functional profile of the identified molecules provides new pathophysiological insight into MS. Future development of these techniques could open up novel applications in terms of molecular diagnosis and therapy monitoring in MS patients.

These results do not support a major role of stress in the development of the disease, but repeated and more focused measures of stress are needed to firmly exclude stress as a potential risk factor for MS.

Our findings, show no correlation between EA, CD and postpartum relapses and disability. Therefore these procedures can safely be applied in MS patients. On the other hand, post-partum relapses are significantly associated with increased disability, which calls for the need of preventive therapies after delivery.